General Information of This Linker
Linker ID
LIN0HGTZQ
Linker Name
Mal-PEG2-Val-Cit-PABA-Cyclization Spacer
Linker Type
Cathepsin-cleavable linker
Antibody-Linker Relation
Cleavable
Structure
Formula
C36H54N8O14
Isosmiles
CC(C)C(NC(=O)OCCOCCN1C(=O)C=CC1=O)C(=O)NC(CCCNC(N)=O)C(=O)Nc1ccc(COC(=O)N(C)CCN(CCOCCO)C(=O)O)cc1
InChI
InChI=1S/C36H54N8O14/c1-24(2)30(41-34(51)57-22-21-56-19-16-44-28(46)10-11-29(44)47)32(49)40-27(5-4-12-38-33(37)50)31(48)39-26-8-6-25(7-9-26)23-58-36(54)42(3)13-14-43(35(52)53)15-18-55-20-17-45/h6-11,24,27,30,45H,4-5,12-23H2,1-3H3,(H,39,48)(H,40,49)(H,41,51)(H,52,53)(H3,37,38,50)
InChIKey
KEQDFILUSXJIIN-UHFFFAOYSA-N
Pharmaceutical Properties
Molecule Weight
822.87
Polar area
297.8
Complexity
58
xlogp Value
-0.1919
Heavy Count
58
Rot Bonds
26
Hbond acc
13
Hbond Donor
7
Each Antibody-drug Conjugate Related to This Linker
Full Information of The Activity Data of The ADC(s) Related to This Linker
Trastuzumab duocarmazine [NDA]
Identified from the Human Clinical Data
Click To Hide/Show 7 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Related Clinical Trial
NCT Number NCT03262935  Clinical Status Phase 3
Clinical Description
A multi-centre, open-label, randomized clinical trial comparing the efficacy and safety of the antibody-drug conjugate SYD985 to physician's choice in patients with HER2-positive unresectable locally advanced or metastatic breast cancer.
Experiment 2 Reporting the Activity Date of This ADC [2]
Related Clinical Trial
NCT Number NCT04205630  Clinical Status Phase 2
Clinical Description
A single-arm phase 2 trial to evaluate the safety and efficacy of the antibody-drug conjugate (ADC) SYD985 in patients with human epidermal growth factor receptor 2 (HER2)-expressing endometrial carcinoma who previously progressed on or after first line platinum-based chemotherapy.
Experiment 3 Reporting the Activity Date of This ADC [3]
Related Clinical Trial
NCT Number NCT01042379  Clinical Status Phase 2
Clinical Description
I-SPY trial (investigation of serial studies to predict your therapeutic response with imaging and molecular analysis 2).
Experiment 4 Reporting the Activity Date of This ADC [4]
Related Clinical Trial
NCT Number NCT04983238  Clinical Status Phase 1
Clinical Description
A multicenter, randomized, double-blind, placebo-controlled trial with a single arm run-in period to evaluate the safety and efficacy of sodium thiosulfate (BYON5667) Eye drops to reduce ocular toxicity in cancer patients treated with SYD985.
Experiment 5 Reporting the Activity Date of This ADC [5]
Related Clinical Trial
NCT Number NCT04602117  Clinical Status Phase 1
Clinical Description
ISPY-P1.01: evaluating the safety of weekly paclitaxel with trastuzumab duocarmazine (SYD985) in patients with metastatic cancer: a phase 1/Ib trial.
Experiment 6 Reporting the Activity Date of This ADC [6]
Related Clinical Trial
NCT Number NCT04235101  Clinical Status Phase 1
Clinical Description
A two-part phase 1 study with the antibody-drug conjugate SYD985 in combination with niraparib to evaluate safety, pharmacokinetics and efficacy in patients with HER2-expressing locally advanced or metastatic solid tumors.
Experiment 7 Reporting the Activity Date of This ADC [7]
Related Clinical Trial
NCT Number NCT02277717  Clinical Status Phase 1
Clinical Description
A two part first-in-human phase 1 study (with expanded cohorts) with the antibody-drug conjugate SYD985 to evaluate the safety, pharmacokinetics and efficacy in patients with locally advanced or metastatic solid tumors.
Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 11 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 33.30% (Day 76) High HER2 expression (HER2+++; IHC 3+; FISH+)
Method Description
All treatments were conducted at day 0 by a single dose, i.v, 3 mg/kg x1 injection into the tail vein, Data, depicted as mean tumour volume, consists of 6-8 animals per experimental group.
In Vivo Model Breast cancer PDX model (PDX: MAXF-1162)
Experiment 2 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 42.90% (Day 80) Low HER2 expression (HER2+; IHC +; FISH-)
Method Description
All treatments were conducted at day 0 by a single dose, i.v, 3 mg/kg x1 injection into the tail vein, Data, depicted as mean tumour volume, consists of 6-8 animals per experimental group.
In Vivo Model Breast cancer PDX model (PDX: MAXF 449)
Experiment 3 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 65.00% (Day 80) Moderate HER2 expression (HER2++; IHC 2+; FISH-)
Method Description
All treatments were conducted at day 0 by a single dose, i.v, 3 mg/kg x1 injection into the tail vein, Data, depicted as mean tumour volume, consists of 6-8 animals per experimental group.
In Vivo Model Breast cancer PDX model (PDX: HBCx-34)
Experiment 4 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 66.70% (Day 31) Moderate HER2 expression (HER2++; IHC 2+; FISH-)
Method Description
All treatments were conducted at day 0 by a single dose, i.v, 3 mg/kg x1 injection into the tail vein, Data, depicted as mean tumour volume, consists of 6-8 animals per experimental group.
In Vivo Model Breast cancer PDX model (PDX: ST313)
Experiment 5 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 75.00% (Day 28) Low HER2 expression (HER2+; IHC +; FISH-)
Method Description
All treatments were conducted at day 0 by a single dose, i.v, 10 mg/kg x1 injection into the tail vein, Data, depicted as mean tumour volume, consists of 6-8 animals per experimental group.
In Vivo Model Gastric cancer PDX model (PDX: GXA3057)
Experiment 6 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 90.00% (Day 46) Moderate HER2 expression (HER2++; IHC 2+; FISH-)
Method Description
All treatments were conducted at day 0 by a single dose, i.v, 10 mg/kg x1 injection into the tail vein, Data, depicted as mean tumour volume, consists of 6-8 animals per experimental group.
In Vivo Model Gastric cancer PDX model (PDX: GXA3038)
Experiment 7 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 20) High HER2 expression (HER2+++; IHC 3+; FISH+)
Method Description
All treatments were conducted at day 0 by a single dose, i.v, 10 mg/kg x1 injection into the tail vein, Data, depicted as mean tumour volume, consists of 6-8 animals per experimental group.
In Vivo Model Gastric cancer PDX model (PDX: GXA3054)
Experiment 8 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 21) Moderate HER2 expression (HER2++; IHC 2+; FISH+)
Method Description
All treatments were conducted at day 0 by a single dose, i.v, 10 mg/kg x1 injection into the tail vein, Data, depicted as mean tumour volume, consists of 6-8 animals per experimental group.
In Vivo Model Gastric cancer PDX model (PDX: GXA3067)
Experiment 9 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 41) High HER2 expression (HER2+++; IHC 3+; FISH+)
Method Description
All treatments were conducted at day 0 by a single dose, i.v, 10 mg/kg x1 injection into the tail vein, Data, depicted as mean tumour volume, consists of 6-8 animals per experimental group.
In Vivo Model Bladder cancer PDX model (PDX: BXF439)
Experiment 10 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 32) Low HER2 expression (HER2+; IHC +; FISH-)
Method Description
All treatments were conducted at day 0 by a single dose, i.v, 3 mg/kg x1 injection into the tail vein, Data, depicted as mean tumour volume, consists of 6-8 animals per experimental group.
In Vivo Model Breast cancer PDX model (PDX: MAXF-MX1)
Experiment 11 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 40) Low HER2 expression (HER2+; IHC +; FISH-)
Method Description
All treatments were conducted at day 0 by a single dose, i.v, 3 mg/kg x1 injection into the tail vein, Data, depicted as mean tumour volume, consists of 6-8 animals per experimental group.
In Vivo Model Breast cancer PDX model (PDX: HBCx-10)
Vobramitamab duocarmazine [Phase 2/3]
Identified from the Human Clinical Data
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [9]
Related Clinical Trial
NCT Number NCT05551117  Clinical Status Phase 2
Clinical Description
A phase 2, randomized, open-label, study of two dose levels of obramitamab duocarmazine in participants with metastatic castration-resistant prostate cancer.
Experiment 2 Reporting the Activity Date of This ADC [10]
Patients Enrolled
Patients of multiple tumor types, which included 3 melanoma patients refractory to 2 prior lines of checkpoint therapy.
Administration Dosage
6 dose cohorts (0.50-4.00 mg/kg) every 3 weeks.
Related Clinical Trial
NCT Number NCT03729596  Clinical Status Phase 1/2
Clinical Description
A phase 1/2, first-in-human, open-label, dose-escalation study of MGC018 (anti-B7-H3 antibody drug conjugate) alone and in combination with MGA012 (anti-PD-1 antibody) in patients with advanced solid tumors.
Experiment 3 Reporting the Activity Date of This ADC [11]
Related Clinical Trial
NCT Number NCT05293496  Clinical Status Phase 1
Clinical Description
A phase 1/1b dose escalation and cohort expansion study of MGC018 in combination with checkpoint inhibitor in participants with advanced solid tumors.
Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 96.10% (Day 21) High MET expression (MET+++; IHC H-score=265)
Method Description
Female Athymic Nude-Foxn1nu from Envigo (head and neck,triple-negative breast cancer models),68 weeks of age,were used for the PDX studies. Low passage tumor fragments were implanted into stock animals. When tumors reached 1.01.5 cm3,they were reimplanted into prestudy animals unilaterally on the left flank. When tumors reached an average tumor volume of 150-300 mm3,animals were matched by tumor volume into treatment or vehicle control groups. Three animals were assigned to each group and dosed intravenously by tail vein injection (10 mL/kg). Tumor volumes were measured twice weekly by calipers. Prostate cancer subcutaneous PDX model treated with MGC018 or control ADC at 3 mg/kg (QW3).

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In Vivo Model Pancreatic cancer PDX model (PDX: PDX-PAX-13565)
Experiment 2 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 97.60% (Day 42) Moderate MET expression (MET++; IHC H-score=130)
Method Description
Male NOG mice from Taconic (prostate cancer model),68 weeks of age,were used for the PDX studies. Low passage tumor fragments were implanted into stock animals. When tumors reached 1.01.5 cm3,they were reimplanted into prestudy animals unilaterally on the left flank. When tumors reached an average tumor volume of 150-300 mm3,animals were matched by tumor volume into treatment or vehicle control groups. Three animals were assigned to each group and dosed intravenously by tail vein injection (10 mL/kg). Tumor volumes were measured twice weekly by calipers. Head and neck cancer subcutaneous PDX model treated with MGC018 or control ADC at 3 mg/kg (Q2W 2).

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In Vivo Model Head and neck cancer PDX model
Experiment 3 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 98.20% (Day 10) High MET expression (MET+++; IHC H-score=240)
Method Description
Female Athymic Nude-Foxn1nu from Envigo (head and neck,triple-negative breast cancer models),68 weeks of age,were used for the PDX studies. Low passage tumor fragments were implanted into stock animals. When tumors reached 1.01.5 cm3,they were reimplanted into prestudy animals unilaterally on the left flank. When tumors reached an average tumor volume of 150-300 mm3,animals were matched by tumor volume into treatment or vehicle control groups. Three animals were assigned to each group and dosed intravenously by tail vein injection (10 mL/kg). Tumor volumes were measured twice weekly by calipers. Triple-negative breast cancer subcutaneous PDX model treated with MGC018 or control ADC at 3 mg/kg (QW2).

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In Vivo Model Triple-negative breast cancer PDX model
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 25 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 22.40% (Day 50) High MET expression (MET+++; IHC H-score=287)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). Calu-6 lung cancer subcutaneous xenografts were treated with MGC018 or control ADC at 0.3 mg/kg QWx4.

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In Vivo Model Lung cancer CDX model
In Vitro Model Lung adenocarcinoma Calu-6 cells CVCL_0236
Experiment 2 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 30.10% (Day 80) Moderate MET expression (MET++; IHC H-score=150)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). PA-1 ovarian cancer subcutaneous xenografts were treated with MGC018 or control ADC at 3 mg/kg as a single dose,QW1.

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In Vivo Model Ovarian cancer CDX model
In Vitro Model Ovarian mixed germ cell tumor PA-1 cells CVCL_0479
Experiment 3 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 42.90% (Day 60) High MET expression (MET+++; IHC H-score=287)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). A-1 ovarian cancer subcutaneous xenografts were treated with MGC018 or control ADC at 3 mg/kg.

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In Vivo Model Ovarian cancer CDX model
In Vitro Model Ovarian mixed germ cell tumor PA-1 cells CVCL_0479
Experiment 4 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 43.90% (Day 100) NegativeCD276 expression (CD276-)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). MDA-MB-468 triple-negative breast cancer orthotopic xenografts were treated with MGC018 or control ADC at 3 mg/kg.

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In Vivo Model Triple-negative breast cancer CDX model
In Vitro Model Breast adenocarcinoma MDA-MB-468 Luc cells CVCL_0419
Experiment 5 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 59.30% (Day 70) High MET expression (MET+++; IHC H-score=255)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). Calu-6 lung cancer subcutaneous xenografts were treated with MGC018 or control ADC at 3 mg/kg.

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In Vivo Model Lung cancer CDX model
In Vitro Model Lung adenocarcinoma Calu-6 cells CVCL_0236
Experiment 6 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 62.70% (Day 100) Moderate MET expression (MET++; IHC H-score=150)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3).MDA-MB-468 triple-negative breast cancer orthotopic xenografts were treated with MGC018 or control ADC at 0.3 mg/kg QW4.

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In Vivo Model Triple-negative breast cancer CDX model
In Vitro Model Breast adenocarcinoma MDA-MB-468 Luc cells CVCL_0419
Experiment 7 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 62.80% (Day 70) High MET expression (MET+++; IHC H-score=287)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). PA-1 ovarian cancer subcutaneous xenografts were treated with MGC018 or control ADC at 0.3 mg/kg QW4.

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In Vivo Model Ovarian cancer CDX model
In Vitro Model Ovarian mixed germ cell tumor PA-1 cells CVCL_0479
Experiment 8 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 66.50% (Day 50) High MET expression (MET+++; IHC H-score=255)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). Calu-6 lung cancer subcutaneous xenografts were treated with MGC018 or control ADC at 3 mg/kg.

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In Vivo Model Lung cancer CDX model
In Vitro Model Lung adenocarcinoma Calu-6 cells CVCL_0236
Experiment 9 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 71.90% (Day 50) High MET expression (MET+++; IHC H-score=255)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). Calu-6 lung cancer subcutaneous xenografts were treated with MGC018 or control ADC at 1 mg/kg QWx4.

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In Vivo Model Lung cancer CDX model
In Vitro Model Lung adenocarcinoma Calu-6 cells CVCL_0236
Experiment 10 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 76.30% (Day 50) High MET expression (MET+++; IHC H-score=255)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). Calu-6 lung cancer subcutaneous xenografts were treated with MGC018 or control ADC at 6 mg/kg.

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In Vivo Model Lung cancer CDX model
In Vitro Model Lung adenocarcinoma Calu-6 cells CVCL_0236
Experiment 11 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 76.60% (Day 60) High MET expression (MET+++; IHC H-score=255)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). A375.S2 melanoma subcutaneous xenografts were treated with MGC018 or control ADC at 0.3 mg/kg QW4.

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In Vivo Model Melanoma CDX model
In Vitro Model Amelanotic melanoma A375.S2 cells CVCL_0136
Experiment 12 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 82.80% (Day 50) High MET expression (MET+++; IHC H-score=255)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). Calu-6 lung cancer subcutaneous xenografts were treated with MGC018 or control ADC at 3 mg/kg QWx4.

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In Vivo Model Lung cancer CDX model
In Vitro Model Lung adenocarcinoma Calu-6 cells CVCL_0236
Experiment 13 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 83.90% (Day 60) High MET expression (MET+++; IHC H-score=265)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). A375.S2 melanoma subcutaneous xenografts were treated with MGC018 or control ADC at 1 mg/kg.

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In Vivo Model Melanoma CDX model
In Vitro Model Amelanotic melanoma A375.S2 cells CVCL_0136
Experiment 14 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 87.50% (Day 50) High MET expression (MET+++; IHC H-score=255)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). Calu-6 lung cancer subcutaneous xenografts were treated with MGC018 or control ADC at 10 mg/kg.

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In Vivo Model Lung cancer CDX model
In Vitro Model Lung adenocarcinoma Calu-6 cells CVCL_0236
Experiment 15 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 88.80% (Day 60) High MET expression (MET+++; IHC H-score=287)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). A-1 ovarian cancer subcutaneous xenografts were treated with MGC018 or control ADC at 6 mg/kg.

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In Vivo Model Ovarian cancer CDX model
In Vitro Model Ovarian mixed germ cell tumor PA-1 cells CVCL_0479
Experiment 16 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 90.50% (Day 60) High MET expression (MET+++; IHC H-score=287)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). A-1 ovarian cancer subcutaneous xenografts were treated with MGC018 or control ADC at 10 mg/kg.

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In Vivo Model Ovarian cancer CDX model
In Vitro Model Ovarian mixed germ cell tumor PA-1 cells CVCL_0479
Experiment 17 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 91.40% (Day 80) High MET expression (MET+++; IHC H-score=287)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). PA-1 ovarian cancer subcutaneous xenografts were treated with MGC018 or control ADC at 3 mg/kg as a single dose,QW4.

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In Vivo Model Ovarian cancer CDX model
In Vitro Model Ovarian mixed germ cell tumor PA-1 cells CVCL_0479
Experiment 18 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 94.60% (Day 70) High MET expression (MET+++; IHC H-score=287)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). PA-1 ovarian cancer subcutaneous xenografts were treated with MGC018 or control ADC at 1 mg/kg QW4.

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In Vivo Model Ovarian cancer CDX model
In Vitro Model Ovarian mixed germ cell tumor PA-1 cells CVCL_0479
Experiment 19 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 96.70% (Day 70) High MET expression (MET+++; IHC H-score=255)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). Calu-6 lung cancer subcutaneous xenografts were treated with MGC018 or control ADC at 6 mg/kg.

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In Vivo Model Lung cancer CDX model
In Vitro Model Lung adenocarcinoma Calu-6 cells CVCL_0236
Experiment 20 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 97.00% (Day 100) Moderate MET expression (MET++; IHC H-score=150)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3).MDA-MB-468 triple-negative breast cancer orthotopic xenografts were treated with MGC018 or control ADC at 1 mg/kg QW4.

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In Vivo Model Triple-negative breast cancer CDX model
In Vitro Model Breast adenocarcinoma MDA-MB-468 Luc cells CVCL_0419
Experiment 21 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 97.60% (Day 80) High MET expression (MET+++; IHC H-score=287)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). PA-1 ovarian cancer subcutaneous xenografts were treated with MGC018 or control ADC at 3 mg/kg as a single dose,Q2W4.

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In Vivo Model Ovarian cancer CDX model
In Vitro Model Ovarian mixed germ cell tumor PA-1 cells CVCL_0479
Experiment 22 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 97.90% (Day 100) Moderate MET expression (MET++; IHC H-score=150)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). MDA-MB-468 triple-negative breast cancer orthotopic xenografts were treated with MGC018 or control ADC at 6 mg/kg.

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In Vivo Model Triple-negative breast cancer CDX model
In Vitro Model Breast adenocarcinoma MDA-MB-468 Luc cells CVCL_0419
Experiment 23 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 98.10% (Day 60) High MET expression (MET+++; IHC H-score=265)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). A375.S2 melanoma subcutaneous xenografts were treated with MGC018 or control ADC at 3 mg/kg.

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In Vivo Model Melanoma CDX model
In Vitro Model Amelanotic melanoma A375.S2 cells CVCL_0136
Experiment 24 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 98.60% (Day 70) High MET expression (MET+++; IHC H-score=255)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). Calu-6 lung cancer subcutaneous xenografts were treated with MGC018 or control ADC at 10 mg/kg.

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In Vivo Model Lung cancer CDX model
In Vitro Model Lung adenocarcinoma Calu-6 cells CVCL_0236
Experiment 25 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 99.70% (Day 60) High MET expression (MET+++; IHC H-score=265)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). A375.S2 melanoma subcutaneous xenografts were treated with MGC018 or control ADC at 1 mg/kg QW4.

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In Vivo Model Melanoma CDX model
In Vitro Model Amelanotic melanoma A375.S2 cells CVCL_0136
Revealed Based on the Cell Line Data
Click To Hide/Show 9 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
181.00 pM
High CD276 expression (CD276+++; 138,000 CD276 molecules/cell)
Method Description
MGC018-mediated in vitro cytotoxicity was evaluated across a set of tumor cell lines representing multiple cancer types expressing varying levels of B7-H3. MDA-MB-468,A375.S2,PA-1,Calu-6,Hs700T,SW48,and LN-229 tumor cell lines were obtained from ATCC and cultured in DMEM/F-12 media containing 10% FBS. NCI-H1703 and Raji tumor cell lines were obtained from ATCC and cultured in RPMI1640 media containing 10% FBS.

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In Vitro Model Amelanotic melanoma A375.S2 cells CVCL_0136
Experiment 2 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
260.00 pM
High CD276 expression (CD276+++; 139,000 CD276 molecules/cell)
Method Description
MGC018-mediated in vitro cytotoxicity was evaluated across a set of tumor cell lines representing multiple cancer types expressing varying levels of B7-H3. MDA-MB-468,A375.S2,PA-1,Calu-6,Hs700T,SW48,and LN-229 tumor cell lines were obtained from ATCC and cultured in DMEM/F-12 media containing 10% FBS. NCI-H1703 and Raji tumor cell lines were obtained from ATCC and cultured in RPMI1640 media containing 10% FBS.

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In Vitro Model Lung adenocarcinoma Calu-6 cells CVCL_0236
Experiment 3 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
275.00 pM
High CD276 expression (CD276+++; 310,000 CD276 molecules/cell)
Method Description
MGC018-mediated in vitro cytotoxicity was evaluated across a set of tumor cell lines representing multiple cancer types expressing varying levels of B7-H3. MDA-MB-468,A375.S2,PA-1,Calu-6,Hs700T,SW48,and LN-229 tumor cell lines were obtained from ATCC and cultured in DMEM/F-12 media containing 10% FBS. NCI-H1703 and Raji tumor cell lines were obtained from ATCC and cultured in RPMI1640 media containing 10% FBS.

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In Vitro Model Ovarian mixed germ cell tumor PA-1 cells CVCL_0479
Experiment 4 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
319.00 pM
High CD276 expression (CD276+++; 122,000 CD276 molecules/cell)
Method Description
MGC018-mediated in vitro cytotoxicity was evaluated across a set of tumor cell lines representing multiple cancer types expressing varying levels of B7-H3. MDA-MB-468,A375.S2,PA-1,Calu-6,Hs700T,SW48,and LN-229 tumor cell lines were obtained from ATCC and cultured in DMEM/F-12 media containing 10% FBS. NCI-H1703 and Raji tumor cell lines were obtained from ATCC and cultured in RPMI1640 media containing 10% FBS.

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In Vitro Model Neoplasm Hs 700T cells CVCL_0858
Experiment 5 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
585.00 pM
Moderate MET expression (MET++; IHC H-score=180)
Method Description
MGC018-mediated in vitro cytotoxicity was evaluated across a set of tumor cell lines representing multiple cancer types expressing varying levels of B7-H3. MDA-MB-468,A375.S2,PA-1,Calu-6,Hs700T,SW48,and LN-229 tumor cell lines were obtained from ATCC and cultured in DMEM/F-12 media containing 10% FBS. NCI-H1703 and Raji tumor cell lines were obtained from ATCC and cultured in RPMI1640 media containing 10% FBS.

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In Vitro Model Lung squamous cell carcinoma NCI-H1703 cells CVCL_1490
Experiment 6 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
767.00 pM
Moderate CD276 expression (CD276++; 57,000 CD276 molecules/cell)
Method Description
MGC018-mediated in vitro cytotoxicity was evaluated across a set of tumor cell lines representing multiple cancer types expressing varying levels of B7-H3. MDA-MB-468,A375.S2,PA-1,Calu-6,Hs700T,SW48,and LN-229 tumor cell lines were obtained from ATCC and cultured in DMEM/F-12 media containing 10% FBS. NCI-H1703 and Raji tumor cell lines were obtained from ATCC and cultured in RPMI1640 media containing 10% FBS.

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In Vitro Model Breast adenocarcinoma MDA-MB-468 cells CVCL_0419
Experiment 7 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
910.00 pM
Moderate CD276 expression (CD276++; 73,700 CD276 molecules/cell)
Method Description
MGC018-mediated in vitro cytotoxicity was evaluated across a set of tumor cell lines representing multiple cancer types expressing varying levels of B7-H3. MDA-MB-468,A375.S2,PA-1,Calu-6,Hs700T,SW48,and LN-229 tumor cell lines were obtained from ATCC and cultured in DMEM/F-12 media containing 10% FBS. NCI-H1703 and Raji tumor cell lines were obtained from ATCC and cultured in RPMI1640 media containing 10% FBS.

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In Vitro Model Glioblastoma LN-229 cells CVCL_0393
Experiment 8 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1447.00 pM
High CD276 expression (CD276+++; 153,000 CD276 molecules/cell)
Method Description
MGC018-mediated in vitro cytotoxicity was evaluated across a set of tumor cell lines representing multiple cancer types expressing varying levels of B7-H3. MDA-MB-468,A375.S2,PA-1,Calu-6,Hs700T,SW48,and LN-229 tumor cell lines were obtained from ATCC and cultured in DMEM/F-12 media containing 10% FBS. NCI-H1703 and Raji tumor cell lines were obtained from ATCC and cultured in RPMI1640 media containing 10% FBS.

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In Vitro Model Colon adenocarcinoma SW48 cells CVCL_1724
Experiment 9 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 10.00 nM Moderate CD276 expression (CD276++; 59,800 CD276 molecules/cell)
Method Description
MGC018-mediated in vitro cytotoxicity was evaluated across a set of tumor cell lines representing multiple cancer types expressing varying levels of B7-H3. MDA-MB-468,A375.S2,PA-1,Calu-6,Hs700T,SW48,and LN-229 tumor cell lines were obtained from ATCC and cultured in DMEM/F-12 media containing 10% FBS. NCI-H1703 and Raji tumor cell lines were obtained from ATCC and cultured in RPMI1640 media containing 10% FBS.

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In Vitro Model EBV-related Burkitt lymphoma Raji cells CVCL_0511
SYD-1875 [Phase 1]
Identified from the Human Clinical Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [13]
Related Clinical Trial
NCT Number NCT04202705  Clinical Status Phase 1
Clinical Description
A first-in-human dose-escalation and expansion study with the antibody-drug conjugate SYD1875 to evaluate the safety, pharmacokinetics and efficacy in patients with 5T4-expressing locally advanced or metastatic solid tumours.
SYD1035 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [14]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 28.40% (Day 69) Positive PSMA expression (PSMA+++/++)
Method Description
Tumours were induced subcutaneously by injecting of 10,000,000 LnCap C4.2 cells in 200 uL of RPMI 1640 containing matrigel into the right flank of male CB17.SCID mice. Treatments were started when the tumors reached a mean volume of 100-200 mm3. Mice were randomized according to their individual tumor volume into groups and received a single i.v, 2 mg/kg inection of anti-PSMA ADC.

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In Vivo Model LNCaP C4-2 CDX model
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 2 Reporting the Activity Date of This ADC [14]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 28.96% (Day 69) Positive PSMA expression (PSMA+++/++)
Method Description
Tumours were induced subcutaneously by injecting of 10,000,000 LnCap C4.2 cells in 200 uL of RPMI 1640 containing matrigel into the right flank of male CB17.SCID mice. Treatments were started when the tumors reached a mean volume of 100-200 mm3. Mice were randomized according to their individual tumor volume into groups and received a single i.v, 10 mg/kg inection of anti-PSMA ADC.

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In Vivo Model LNCaP C4-2 CDX model
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Revealed Based on the Cell Line Data
Click To Hide/Show 5 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
82.00%
Positive PSMA expression (PSMA+++/++)
Method Description
LNCaP C4-2 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 2 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
96.00%
Negative PSMA expression (PSMA-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, PSMA-negative DU-145 cells (1,000 cells/well) was cultured with the ADCs for 6 days,and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

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In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 3 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.14 nM
Positive PSMA expression (PSMA+++/++)
Method Description
LNCaP C4-2 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 4 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.38 nM
Negative PSMA expression (PSMA-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, PSMA-negative DU-145 cells (1,000 cells/well) was cultured with the ADCs for 6 days,and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

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In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 5 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 70.00 nM Negative PSMA expression (PSMA-)
Method Description
DU-145 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
SYD998 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [14]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 35.67% (Day 69) Positive PSMA expression (PSMA+++/++)
Method Description
Tumours were induced subcutaneously by injecting of 10,000,000 LnCap C4.2 cells in 200 uL of RPMI 1640 containing matrigel into the right flank of male CB17.SCID mice. Treatments were started when the tumors reached a mean volume of 100-200 mm3. Mice were randomized according to their individual tumor volume into groups and received a single i.v, 2 mg/kg inection of anti-PSMA ADC.

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In Vivo Model LNCaP C4-2 CDX model
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 2 Reporting the Activity Date of This ADC [14]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 94.68% (Day 69) Positive PSMA expression (PSMA+++/++)
Method Description
Tumours were induced subcutaneously by injecting of 10,000,000 LnCap C4.2 cells in 200 uL of RPMI 1640 containing matrigel into the right flank of male CB17.SCID mice. Treatments were started when the tumors reached a mean volume of 100-200 mm3. Mice were randomized according to their individual tumor volume into groups and received a single i.v, 10 mg/kg inection of anti-PSMA ADC.

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In Vivo Model LNCaP C4-2 CDX model
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Revealed Based on the Cell Line Data
Click To Hide/Show 5 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
82.00%
Positive PSMA expression (PSMA+++/++)
Method Description
LNCaP C4-2 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 2 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
97.00%
Negative PSMA expression (PSMA-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, PSMA-negative DU-145 cells (1,000 cells/well) was cultured with the ADCs for 6 days,and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

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In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 3 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.23 nM
Positive PSMA expression (PSMA+++/++)
Method Description
LNCaP C4-2 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 4 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.70 nM
Negative PSMA expression (PSMA-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, PSMA-negative DU-145 cells (1,000 cells/well) was cultured with the ADCs for 6 days,and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

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In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 5 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 70.00 nM Negative PSMA expression (PSMA-)
Method Description
DU-145 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
hmAb-C-DUBA [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 17 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [15]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 42.39% (Day 59) Moderate CD276 expression (CD276 ++)
Method Description
PA-1 cells were subcutaneously implanted into groups of mice(n=7), which then received a single dose of hmAb-C-DUBA or Ctrl-DUBA (3 mg/kg) at Day 20.
In Vivo Model PA-1 CDX model
In Vitro Model Ovarian mixed germ cell tumor PA-1 cells CVCL_0479
Experiment 2 Reporting the Activity Date of This ADC [15]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 43.85% (Day 70) Moderate CD276 expression (CD276 ++)
Method Description
PA-1 cells were subcutaneously implanted into groups of mice(n=7), which then received a single dose of hmAb-C-DUBA or Ctrl-DUBA (3 mg/kg) at Day 20.
In Vivo Model PA-1 CDX model
In Vitro Model Ovarian mixed germ cell tumor PA-1 cells CVCL_0479
Experiment 3 Reporting the Activity Date of This ADC [15]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 49.48% (Day 110) Moderate CD276 expression (CD276 ++)
Method Description
MDA-MB-468 cells were subcutaneously implanted into groups of mice(n=7), which then received a single dose of hmAb-C-DUBA or Ctrl-DUBA (3 mg/kg) at Day 20.
In Vivo Model MDA-MB-468 CDX model
In Vitro Model Breast adenocarcinoma MDA-MB-468 cells CVCL_0419
Experiment 4 Reporting the Activity Date of This ADC [15]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 59.20% (Day 54) Moderate CD276 expression (CD276 ++)
Method Description
Calu-6 non-small cell lung carcinoma cells were subcutaneously implanted into groups of mice(n=7), which then received a single dose of hmAb-C-DUBA or Ctrl-DUBA (3 mg/kg) at Day 20.
In Vivo Model Calu-6 CDX model
In Vitro Model Lung adenocarcinoma Calu-6 cells CVCL_0236
Experiment 5 Reporting the Activity Date of This ADC [15]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 76.07% (Day 70) Moderate CD276 expression (CD276 ++)
Method Description
PA-1 cells were subcutaneously implanted into groups of mice(n=7), which then received a single dose of hmAb-C-DUBA or Ctrl-DUBA (10 mg/kg) at Day 20.
In Vivo Model PA-1 CDX model
In Vitro Model Ovarian mixed germ cell tumor PA-1 cells CVCL_0479
Experiment 6 Reporting the Activity Date of This ADC [15]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 83.49% (Day 70) Moderate CD276 expression (CD276 ++)
Method Description
PA-1 cells were subcutaneously implanted into groups of mice(n=7), which then received a single dose of hmAb-C-DUBA or Ctrl-DUBA (10 mg/kg x 2) at Day 20.
In Vivo Model PA-1 CDX model
In Vitro Model Ovarian mixed germ cell tumor PA-1 cells CVCL_0479
Experiment 7 Reporting the Activity Date of This ADC [15]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 84.42% (Day 62) Moderate CD276 expression (CD276 ++)
Method Description
Calu-6 non-small cell lung carcinoma cells were subcutaneously implanted intogroups of mice (n=5) essentially, which then received doses of hmAb-C-DUBA (1 mg/kg x 3) at Day 24, 31, 38 and 45 post inoculation, and the animals were evaluated for tumor volume for up to 62 days.
In Vivo Model Calu-6 CDX model
In Vitro Model Lung adenocarcinoma Calu-6 cells CVCL_0236
Experiment 8 Reporting the Activity Date of This ADC [15]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 85.17% (Day 61) Moderate CD276 expression (CD276 ++)
Method Description
A375.52 cells were subcutaneously implanted into groups of mice(n=7), which then received a single dose of hmAb-C-DUBA or Ctrl-DUBA (3 mg/kg) at Day 20.
In Vivo Model A375.52 CDX model
In Vitro Model Amelanotic melanoma A375.S2 cells CVCL_0136
Experiment 9 Reporting the Activity Date of This ADC [15]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 88.65% (Day 59) Moderate CD276 expression (CD276 ++)
Method Description
PA-1 cells were subcutaneously implanted into groups of mice(n=7), which then received a single dose of hmAb-C-DUBA or Ctrl-DUBA (10 mg/kg) at Day 20.
In Vivo Model PA-1 CDX model
In Vitro Model Ovarian mixed germ cell tumor PA-1 cells CVCL_0479
Experiment 10 Reporting the Activity Date of This ADC [15]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 90.47% (Day 62) Moderate CD276 expression (CD276 ++)
Method Description
Calu-6 non-small cell lung carcinoma cells were subcutaneously implanted intogroups of mice (n=5) essentially, which then received doses of hmAb-C-DUBA (3 mg/kg x 3) at Day 24, 31, 38 and 45 post inoculation, and the animals were evaluated for tumor volume for up to 62 days.
In Vivo Model Calu-6 CDX model
In Vitro Model Lung adenocarcinoma Calu-6 cells CVCL_0236
Experiment 11 Reporting the Activity Date of This ADC [15]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 91.81% (Day 54) Moderate CD276 expression (CD276 ++)
Method Description
Calu-6 non-small cell lung carcinoma cells were subcutaneously implanted into groups of mice(n=7), which then received a single dose of hmAb-C-DUBA or Ctrl-DUBA (10 mg/kg) at Day 20.
In Vivo Model Calu-6 CDX model
In Vitro Model Lung adenocarcinoma Calu-6 cells CVCL_0236
Experiment 12 Reporting the Activity Date of This ADC [15]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 92.95% (Day 59) Moderate CD276 expression (CD276 ++)
Method Description
PA-1 cells were subcutaneously implanted into groups of mice(n=7), which then received a single dose of hmAb-C-DUBA or Ctrl-DUBA (6 mg/kg) at Day 20.
In Vivo Model PA-1 CDX model
In Vitro Model Ovarian mixed germ cell tumor PA-1 cells CVCL_0479
Experiment 13 Reporting the Activity Date of This ADC [15]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 97.20% (Day 62) Moderate CD276 expression (CD276 ++)
Method Description
Calu-6 non-small cell lung carcinoma cells were subcutaneously implanted intogroups of mice (n=5) essentially, which then received doses of hmAb-C-DUBA (6 mg/kg x 3) at Day 24, 31, 38 and 45 post inoculation, and the animals were evaluated for tumor volume for up to 62 days.
In Vivo Model Calu-6 CDX model
In Vitro Model Lung adenocarcinoma Calu-6 cells CVCL_0236
Experiment 14 Reporting the Activity Date of This ADC [15]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 98.30% (Day 100) Moderate CD276 expression (CD276 ++)
Method Description
MDA-MB-468 cells were subcutaneously implanted intogroups of mice (n=5) essentially, which then received doses of hmAb-C-DUBA (3 mg/kg x 3), and the animals were evaluated for tumor volume for up to 110 days.
In Vivo Model MDA-MB-468 CDX model
In Vitro Model Breast adenocarcinoma MDA-MB-468 cells CVCL_0419
Experiment 15 Reporting the Activity Date of This ADC [15]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 98.92% (Day 61) Moderate CD276 expression (CD276 ++)
Method Description
A375.52 cells were subcutaneously implanted into groups of mice(n=7), which then received a single dose of hmAb-C-DUBA or Ctrl-DUBA (6 mg/kg) at Day 20.
In Vivo Model A375.52 CDX model
In Vitro Model Amelanotic melanoma A375.S2 cells CVCL_0136
Experiment 16 Reporting the Activity Date of This ADC [15]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 98.97% (Day 110) Moderate CD276 expression (CD276 ++)
Method Description
MDA-MB-468 cells were subcutaneously implanted into groups of mice(n=7), which then received a single dose of hmAb-C-DUBA or Ctrl-DUBA (6 mg/kg) at Day 20.
In Vivo Model MDA-MB-468 CDX model
In Vitro Model Breast adenocarcinoma MDA-MB-468 cells CVCL_0419
Experiment 17 Reporting the Activity Date of This ADC [15]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 99.24% (Day 70) Moderate CD276 expression (CD276 ++)
Method Description
PA-1 cells were subcutaneously implanted into groups of mice(n=7), which then received a single dose of hmAb-C-DUBA or Ctrl-DUBA (10 mg/kg x 4) at Day 20.
In Vivo Model PA-1 CDX model
In Vitro Model Ovarian mixed germ cell tumor PA-1 cells CVCL_0479
WO2015177360A1 ADC-LC41 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [14]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 43.85% (Day 47) Positive 5T4 expression (5T4+++/++)
Method Description
Tumours were induced subcutaneously by injecting of 10,000,000 PA-1 cells in 100 uL of RPMI 1640 containing matrigel into the right flank of male Balb/c nude mice. Treatments were started when the tumors reached a mean volume of 200-300 mm3. Mice were randomized according to their individual tumor volume into groups and received a single i.v, 3 mg/kg inection of anti-5T4 ADC.

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In Vivo Model PA-1 CDX model
In Vitro Model Ovarian mixed germ cell tumor PA-1 cells CVCL_0479
Experiment 2 Reporting the Activity Date of This ADC [14]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 85.04% (Day 47) Positive 5T4 expression (5T4+++/++)
Method Description
Tumours were induced subcutaneously by injecting of 10,000,000 PA-1 cells in 100 uL of RPMI 1640 containing matrigel into the right flank of male Balb/c nude mice. Treatments were started when the tumors reached a mean volume of 200-300 mm3. Mice were randomized according to their individual tumor volume into groups and received a single i.v, 10 mg/kg inection of anti-5T4 ADC.

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In Vivo Model PA-1 CDX model
In Vitro Model Ovarian mixed germ cell tumor PA-1 cells CVCL_0479
Revealed Based on the Cell Line Data
Click To Hide/Show 10 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
50.00%
Negative PSMA expression (PSMA-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, PSMA-negative DU-145 cells (1,000 cells/well) was cultured with the ADCs for 6 days,and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

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In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 2 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
80.00%
Positive PSMA expression (PSMA+++/++)
Method Description
LNCaP C4-2 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 3 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
91.00%
Positive 5T4 expression (5T4+++/++)
Method Description
MDA-MB-468 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Breast adenocarcinoma MDA-MB-468 cells CVCL_0419
Experiment 4 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
98.00%
Negative 5T4 expression (5T4-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, 5T4-negative SK-MEL-30 cells (2,000 cells/well) was cultured with the ADCs for 6 days, and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

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In Vitro Model Cutaneous melanoma SK-MEL-30 cells CVCL_0039
Experiment 5 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.09 nM
Positive 5T4 expression (5T4+++/++)
Method Description
MDA-MB-468 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Breast adenocarcinoma MDA-MB-468 cells CVCL_0419
Experiment 6 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.31 nM
Positive PSMA expression (PSMA+++/++)
Method Description
LNCaP C4-2 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 7 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.35 nM
Negative 5T4 expression (5T4-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, 5T4-negative SK-MEL-30 cells (2,000 cells/well) was cultured with the ADCs for 6 days, and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

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In Vitro Model Cutaneous melanoma SK-MEL-30 cells CVCL_0039
Experiment 8 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 10.00 nM Negative PSMA expression (PSMA-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, PSMA-negative DU-145 cells (1,000 cells/well) was cultured with the ADCs for 6 days,and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

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In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 9 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 70.00 nM Negative PSMA expression (PSMA-)
Method Description
DU-145 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 10 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 90.00 nM Negative 5T4 expression (5T4-)
Method Description
SK-MEL-30 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Cutaneous melanoma SK-MEL-30 cells CVCL_0039
SYD1091 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [14]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 67.53% (Day 69) Positive PSMA expression (PSMA+++/++)
Method Description
Tumours were induced subcutaneously by injecting of 10,000,000 LnCap C4.2 cells in 200 uL of RPMI 1640 containing matrigel into the right flank of male CB17.SCID mice. Treatments were started when the tumors reached a mean volume of 100-200 mm3. Mice were randomized according to their individual tumor volume into groups and received a single i.v, 2 mg/kg inection of anti-PSMA ADC.

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In Vivo Model LNCaP C4-2 CDX model
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 2 Reporting the Activity Date of This ADC [14]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 93.44% (Day 69) Positive PSMA expression (PSMA+++/++)
Method Description
Tumours were induced subcutaneously by injecting of 10,000,000 LnCap C4.2 cells in 200 uL of RPMI 1640 containing matrigel into the right flank of male CB17.SCID mice. Treatments were started when the tumors reached a mean volume of 100-200 mm3. Mice were randomized according to their individual tumor volume into groups and received a single i.v, 10 mg/kg inection of anti-PSMA ADC.

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In Vivo Model LNCaP C4-2 CDX model
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Revealed Based on the Cell Line Data
Click To Hide/Show 5 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
59.00%
Negative PSMA expression (PSMA-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, PSMA-negative DU-145 cells (1,000 cells/well) was cultured with the ADCs for 6 days,and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

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In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 2 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
78.00%
Positive PSMA expression (PSMA+++/++)
Method Description
LNCaP C4-2 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 3 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.25 nM
Positive PSMA expression (PSMA+++/++)
Method Description
LNCaP C4-2 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 4 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
5.00 nM
Negative PSMA expression (PSMA-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, PSMA-negative DU-145 cells (1,000 cells/well) was cultured with the ADCs for 6 days,and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

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In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 5 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 70.00 nM Negative PSMA expression (PSMA-)
Method Description
DU-145 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
WO2015177360A1 ADC-H8-HC41 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [14]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 72.01% (Day 47) Positive 5T4 expression (5T4+++/++)
Method Description
Tumours were induced subcutaneously by injecting of 10,000,000 PA-1 cells in 100 uL of RPMI 1640 containing matrigel into the right flank of male Balb/c nude mice. Treatments were started when the tumors reached a mean volume of 200-300 mm3. Mice were randomized according to their individual tumor volume into groups and received a single i.v, 3 mg/kg inection of anti-5T4 ADC.

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In Vivo Model PA-1 CDX model
In Vitro Model Ovarian mixed germ cell tumor PA-1 cells CVCL_0479
Experiment 2 Reporting the Activity Date of This ADC [14]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 86.18% (Day 47) Positive 5T4 expression (5T4+++/++)
Method Description
Tumours were induced subcutaneously by injecting of 10,000,000 PA-1 cells in 100 uL of RPMI 1640 containing matrigel into the right flank of male Balb/c nude mice. Treatments were started when the tumors reached a mean volume of 200-300 mm3. Mice were randomized according to their individual tumor volume into groups and received a single i.v, 10 mg/kg inection of anti-5T4 ADC.

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In Vivo Model PA-1 CDX model
In Vitro Model Ovarian mixed germ cell tumor PA-1 cells CVCL_0479
Revealed Based on the Cell Line Data
Click To Hide/Show 5 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
88.00%
Positive 5T4 expression (5T4+++/++)
Method Description
MDA-MB-468 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Breast adenocarcinoma MDA-MB-468 cells CVCL_0419
Experiment 2 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
98.00%
Negative 5T4 expression (5T4-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, 5T4-negative SK-MEL-30 cells (2,000 cells/well) was cultured with the ADCs for 6 days, and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

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In Vitro Model Cutaneous melanoma SK-MEL-30 cells CVCL_0039
Experiment 3 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.07 nM
Positive 5T4 expression (5T4+++/++)
Method Description
MDA-MB-468 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Breast adenocarcinoma MDA-MB-468 cells CVCL_0419
Experiment 4 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.27 nM
Negative 5T4 expression (5T4-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, 5T4-negative SK-MEL-30 cells (2,000 cells/well) was cultured with the ADCs for 6 days, and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

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In Vitro Model Cutaneous melanoma SK-MEL-30 cells CVCL_0039
Experiment 5 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 90.00 nM Negative 5T4 expression (5T4-)
Method Description
SK-MEL-30 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Cutaneous melanoma SK-MEL-30 cells CVCL_0039
WO2015177360A1 ADC-HC375 [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 5 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
45.00%
Negative PSMA expression (PSMA-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, PSMA-negative DU-145 cells (1,000 cells/well) was cultured with the ADCs for 6 days,and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

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In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 2 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
81.00%
Positive PSMA expression (PSMA+++/++)
Method Description
LNCaP C4-2 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 3 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.25 nM
Positive PSMA expression (PSMA+++/++)
Method Description
LNCaP C4-2 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 4 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 10.00 nM Negative PSMA expression (PSMA-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, PSMA-negative DU-145 cells (1,000 cells/well) was cultured with the ADCs for 6 days,and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

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In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 5 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 70.00 nM Negative PSMA expression (PSMA-)
Method Description
DU-145 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
WO2015177360A1 ADC-HC152 [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 5 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
50.00%
Negative PSMA expression (PSMA-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, PSMA-negative DU-145 cells (1,000 cells/well) was cultured with the ADCs for 6 days,and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

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In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 2 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
78.00%
Positive PSMA expression (PSMA+++/++)
Method Description
LNCaP C4-2 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 3 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.44 nM
Positive PSMA expression (PSMA+++/++)
Method Description
LNCaP C4-2 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 4 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 10.00 nM Negative PSMA expression (PSMA-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, PSMA-negative DU-145 cells (1,000 cells/well) was cultured with the ADCs for 6 days,and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

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In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 5 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 70.00 nM Negative PSMA expression (PSMA-)
Method Description
DU-145 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
WO2015177360A1 ADC-LC40 [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 20 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
50.00%
Negative PSMA expression (PSMA-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, PSMA-negative DU-145 cells (1,000 cells/well) was cultured with the ADCs for 6 days,and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

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In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 2 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
79.00%
Positive PSMA expression (PSMA+++/++)
Method Description
LNCaP C4-2 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 3 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
80.00%
Positive PSMA expression (PSMA+++/++)
Method Description
LNCaP C4-2 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 4 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
82.00%
Positive PSMA expression (PSMA+++/++)
Method Description
LNCaP C4-2 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 5 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
83.00%
Positive PSMA expression (PSMA+++/++)
Method Description
LNCaP C4-2 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 6 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
96.00%
Negative PSMA expression (PSMA-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, PSMA-negative DU-145 cells (1,000 cells/well) was cultured with the ADCs for 6 days,and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

   Click to Show/Hide
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 7 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
97.00%
Negative PSMA expression (PSMA-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, PSMA-negative DU-145 cells (1,000 cells/well) was cultured with the ADCs for 6 days,and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

   Click to Show/Hide
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 8 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
98.00%
Negative PSMA expression (PSMA-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, PSMA-negative DU-145 cells (1,000 cells/well) was cultured with the ADCs for 6 days,and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

   Click to Show/Hide
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 9 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.17 nM
Positive PSMA expression (PSMA+++/++)
Method Description
LNCaP C4-2 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 10 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.24 nM
Positive PSMA expression (PSMA+++/++)
Method Description
LNCaP C4-2 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 11 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.26 nM
Negative PSMA expression (PSMA-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, PSMA-negative DU-145 cells (1,000 cells/well) was cultured with the ADCs for 6 days,and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

   Click to Show/Hide
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 12 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.30 nM
Positive PSMA expression (PSMA+++/++)
Method Description
LNCaP C4-2 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 13 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.48 nM
Negative PSMA expression (PSMA-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, PSMA-negative DU-145 cells (1,000 cells/well) was cultured with the ADCs for 6 days,and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

   Click to Show/Hide
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 14 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.51 nM
Positive PSMA expression (PSMA+++/++)
Method Description
LNCaP C4-2 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 15 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
2.11 nM
Negative PSMA expression (PSMA-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, PSMA-negative DU-145 cells (1,000 cells/well) was cultured with the ADCs for 6 days,and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

   Click to Show/Hide
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 16 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 10.00 nM Negative PSMA expression (PSMA-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, PSMA-negative DU-145 cells (1,000 cells/well) was cultured with the ADCs for 6 days,and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

   Click to Show/Hide
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 17 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 70.00 nM Negative PSMA expression (PSMA-)
Method Description
DU-145 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 18 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 70.00 nM Negative PSMA expression (PSMA-)
Method Description
DU-145 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 19 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 70.00 nM Negative PSMA expression (PSMA-)
Method Description
DU-145 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 20 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 70.00 nM Negative PSMA expression (PSMA-)
Method Description
DU-145 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
WO2015177360A1 ADC-HC236 [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 5 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
76.00%
Positive PSMA expression (PSMA+++/++)
Method Description
LNCaP C4-2 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 2 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
100.00%
Negative PSMA expression (PSMA-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, PSMA-negative DU-145 cells (1,000 cells/well) was cultured with the ADCs for 6 days,and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

   Click to Show/Hide
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 3 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.22 nM
Positive PSMA expression (PSMA+++/++)
Method Description
LNCaP C4-2 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 4 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
2.08 nM
Negative PSMA expression (PSMA-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, PSMA-negative DU-145 cells (1,000 cells/well) was cultured with the ADCs for 6 days,and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

   Click to Show/Hide
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 5 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 70.00 nM Negative PSMA expression (PSMA-)
Method Description
DU-145 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
WO2015177360A1 ADC-HC153 [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 5 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
79.00%
Positive PSMA expression (PSMA+++/++)
Method Description
LNCaP C4-2 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 2 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
98.00%
Negative PSMA expression (PSMA-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, PSMA-negative DU-145 cells (1,000 cells/well) was cultured with the ADCs for 6 days,and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

   Click to Show/Hide
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 3 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.34 nM
Positive PSMA expression (PSMA+++/++)
Method Description
LNCaP C4-2 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 4 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.76 nM
Negative PSMA expression (PSMA-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, PSMA-negative DU-145 cells (1,000 cells/well) was cultured with the ADCs for 6 days,and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

   Click to Show/Hide
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 5 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 70.00 nM Negative PSMA expression (PSMA-)
Method Description
DU-145 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
WO2015177360A1 ADC-HC247 [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 5 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
82.00%
Positive PSMA expression (PSMA+++/++)
Method Description
LNCaP C4-2 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 2 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
99.00%
Negative PSMA expression (PSMA-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, PSMA-negative DU-145 cells (1,000 cells/well) was cultured with the ADCs for 6 days,and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

   Click to Show/Hide
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 3 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.10 nM
Positive PSMA expression (PSMA+++/++)
Method Description
LNCaP C4-2 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 4 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
2.01 nM
Negative PSMA expression (PSMA-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, PSMA-negative DU-145 cells (1,000 cells/well) was cultured with the ADCs for 6 days,and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

   Click to Show/Hide
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 5 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 70.00 nM Negative PSMA expression (PSMA-)
Method Description
DU-145 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
WO2015177360A1 ADC-HC376 [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 5 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
82.00%
Positive PSMA expression (PSMA+++/++)
Method Description
LNCaP C4-2 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 2 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
98.00%
Negative PSMA expression (PSMA-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, PSMA-negative DU-145 cells (1,000 cells/well) was cultured with the ADCs for 6 days,and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

   Click to Show/Hide
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 3 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.20 nM
Positive PSMA expression (PSMA+++/++)
Method Description
LNCaP C4-2 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 4 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.60 nM
Negative PSMA expression (PSMA-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, PSMA-negative DU-145 cells (1,000 cells/well) was cultured with the ADCs for 6 days,and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

   Click to Show/Hide
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 5 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 70.00 nM Negative PSMA expression (PSMA-)
Method Description
DU-145 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
WO2015177360A1 ADC-HC339 [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 5 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
83.00%
Positive PSMA expression (PSMA+++/++)
Method Description
LNCaP C4-2 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 2 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
99.00%
Negative PSMA expression (PSMA-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, PSMA-negative DU-145 cells (1,000 cells/well) was cultured with the ADCs for 6 days,and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

   Click to Show/Hide
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 3 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.12 nM
Positive PSMA expression (PSMA+++/++)
Method Description
LNCaP C4-2 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Lymph node metastasis of prostate carcinoma LNCaP C4-2 cells CVCL_4782
Experiment 4 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
5.00 nM
Negative PSMA expression (PSMA-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, PSMA-negative DU-145 cells (1,000 cells/well) was cultured with the ADCs for 6 days,and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

   Click to Show/Hide
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
Experiment 5 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 70.00 nM Negative PSMA expression (PSMA-)
Method Description
DU-145 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Prostate carcinoma DU145 cells CVCL_0105
WO2015177360A1 ADC-H8-HC40 [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 5 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
88.00%
Positive 5T4 expression (5T4+++/++)
Method Description
MDA-MB-468 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Breast adenocarcinoma MDA-MB-468 cells CVCL_0419
Experiment 2 Reporting the Activity Date of This ADC [14]
Efficacy Data Max inhibition rate (MIR)
93.00%
Negative 5T4 expression (5T4-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, 5T4-negative SK-MEL-30 cells (2,000 cells/well) was cultured with the ADCs for 6 days, and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

   Click to Show/Hide
In Vitro Model Cutaneous melanoma SK-MEL-30 cells CVCL_0039
Experiment 3 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.07 nM
Positive 5T4 expression (5T4+++/++)
Method Description
MDA-MB-468 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Breast adenocarcinoma MDA-MB-468 cells CVCL_0419
Experiment 4 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.98 nM
Negative 5T4 expression (5T4-)
Method Description
To assess the sensitivity towards cathepsin B, the ADCs were treated for 2 minutes and 4 hours with activated cathepsin B. To measure release of the respective free toxins DUBA or MMAE, 5T4-negative SK-MEL-30 cells (2,000 cells/well) was cultured with the ADCs for 6 days, and the cell viability was measured after 6 days using the CellTiter-GloTM (CTG) assay kit.

   Click to Show/Hide
In Vitro Model Cutaneous melanoma SK-MEL-30 cells CVCL_0039
Experiment 5 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 90.00 nM Negative 5T4 expression (5T4-)
Method Description
SK-MEL-30 cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Cutaneous melanoma SK-MEL-30 cells CVCL_0039
References
Ref 1 A Multi-centre, Open-label, Randomized Clinical Trial Comparing the Efficacy and Safety of the Antibody-drug Conjugate SYD985 to Physician's Choice in Patients With HER2-positive Unresectable Locally Advanced or Metastatic Breast Cancer, NCT03262935
Ref 2 A Single-arm Phase II Trial to Evaluate the Safety and Efficacy of the Antibody-Drug Conjugate (ADC) SYD985 in Patients With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Endometrial Carcinoma Who Previously Progressed on or After First Line Platinum-based Chemotherapy, NCT04205630
Ref 3 I-SPY Trial (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2), NCT01042379
Ref 4 A Multicenter, Randomized, Double-blind, Placebo-controlled Trial With a Single Arm run-in Period to Evaluate the Safety and Efficacy of Sodium Thiosulfate (BYON5667) Eye Drops to Reduce Ocular Toxicity in Cancer Patients Treated With SYD985, NCT04983238
Ref 5 ISPY-P1.01: Evaluating the Safety of Weekly Paclitaxel With Trastuzumab Duocarmazine (SYD985) in Patients With Metastatic Cancer: A Phase I/Ib Trial, NCT04602117
Ref 6 A Two-part Phase I Study With the Antibody-drug Conjugate SYD985 in Combination With Niraparib to Evaluate Safety, Pharmacokinetics and Efficacy in Patients With HER2-expressing Locally Advanced or Metastatic Solid Tumors. NCT04235101
Ref 7 A Two Part First-in-human Phase I Study (With Expanded Cohorts) With the Antibody-drug Conjugate SYD985 to Evaluate the Safety, Pharmacokinetics and Efficacy in Patients With Locally Advanced or Metastatic Solid Tumors, NCT02277717
Ref 8 Anti-integrin immunoconjugates, methods and uses.
Ref 9 A Phase 2, Randomized, Open-label, Study of Two Dose Levels of Obramitamab Duocarmazine in Participants With Metastatic Castration-resistant Prostate Cancer, NCT05551117
Ref 10 Zilovertamab vedotin (MK 2140) in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): Early results from the phase 2 waveLINE-004 study. J Clin Oncol. 2023 41:16_suppl, 7531-7531.
Ref 11 A Phase 1/1b Dose Escalation and Cohort Expansion Study of MGC018 in Combination With Checkpoint Inhibitor in Participants With Advanced Solid Tumors, NCT05293496
Ref 12 Preclinical Development of MGC018, a Duocarmycin-based Antibody-drug Conjugate Targeting B7-H3 for Solid Cancer. Mol Cancer Ther. 2020 Nov;19(11):2235-2244.
Ref 13 A First-in-human Dose-escalation and Expansion Study With the Antibody-drug Conjugate SYD1875 to Evaluate the Safety, Pharmacokinetics and Efficacy in Patients With 5T4-expressing Locally Advanced or Metastatic Solid Tumours
Ref 14 Site-specific conjugation of linker drugs to antibodies and resulting adcs.
Ref 15 Novel b7-h3 binding molecules, antibody drug conjugates thereof and methods of use thereof; 2017-10-19.

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