General Information of This Linker
Linker ID
LIN0QDUUQ
Linker Name
N-succinimidyl 4-(2-pyridyldithio) pentanoate (SPP)
Linker Type
Thiol-sensitive linker
Antibody-Linker Relation
Cleavable
Structure
Formula
C14H16N2O4S2
Isosmiles
CC(CCC(=O)ON1C(=O)CCC1=O)SSC2=CC=CC=N2
PubChem CID
11588139
InChI
InChI=1S/C14H16N2O4S2/c1-10(21-22-11-4-2-3-9-15-11)5-8-14(19)20-16-12(17)6-7-13(16)18/h2-4,9-10H,5-8H2,1H3
InChIKey
GTBCXYYVWHFQRS-UHFFFAOYSA-N
IUPAC Name
(2,5-dioxopyrrolidin-1-yl) 4-(pyridin-2-yldisulfanyl)pentanoate
Pharmaceutical Properties
Molecule Weight
340.4
Polar area
127
Complexity
417
xlogp Value
1.5
Heavy Count
22
Rot Bonds
8
Hbond acc
7
Hbond Donor
0
Each Antibody-drug Conjugate Related to This Linker
Full Information of The Activity Data of The ADC(s) Related to This Linker
Lorvotuzumab mertansine [Phase 2 (discontinued)]
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]
Patients Enrolled
Eligible patients include adults (≥18) with CD56+ hematologic malignancies (AML, high-risk MDS, NK leukemia, ALL, CML blast phase, MF, or BPDCN) refractory to prior therapies, ECOG ≤2, adequate organ function, and proper contraception. Exclusions: IMGN901 allergy/hypersensitivity, active CNS disease, grade ≥3 neuropathy, uncontrolled cardiac/pulmonary/pancreatic conditions, recent major surgery, pregnancy, or protocol non-compliance. Reproductive-age participants must use dual contraception.

   Click to Show/Hide
Administration Dosage
100 mg/m2 by vein on Day 1 and 8 of a 21-day cycle.
Related Clinical Trial
NCT Number NCT02420873  Clinical Status PHASE2
Clinical Description
An Open-label Phase II Study of Lorvotuzumab Mertansine (IMGN901) in CD56 Expressing Hematological Malignancies
Primary Endpoint
The primary endpoint is Overall Response Rate (ORR) to IMGN901 in CD56+ hematological malignancies, defined as Complete Remission (CR + CRp + CRi) achieved within three cycles (53-day evaluation).
Other Endpoint
Secondary data collection focuses on safety monitoring but specific endpoints were not predefined in the provided information.
Experiment 2 Reporting the Activity Date of This ADC [2]
Patients Enrolled
Eligible patients must have histologically confirmed, relapsed/refractory CD56+ multiple myeloma (≥1 prior therapy, ≤6 regimens at MTD). Key inclusion: ECOG 0-2, adequate organ function, life expectancy ≥12 weeks, no severe neuropathy, cardiac disease, pancreatitis, or active infections. Exclusion: recent stroke, malignancies (except certain in situ cancers), uncontrolled comorbidities, or prior hypersensitivity to monoclonal antibodies. Prior therapy washout: ≥4 weeks for chemo/RT/surgery, ≥2 weeks for biologics. Concurrent bisphosphonates allowed if stable; steroids restricted to specific indications.

   Click to Show/Hide
Administration Dosage
dose escalation study, doses will vary per cohort. patients will receive an IV infusion weekly for two weeks every three weeks.
Related Clinical Trial
NCT Number NCT00346255  Clinical Status PHASE1
Clinical Description
A Phase I Study to Assess The Safety and Pharmacokinetics of BB-10901 (huN901-DM1) Given as an Intravenous Infusion Weekly for Two Consecutive Weeks Every Three Weeks to Subjects With Relapsed and Relapsed Refractory CD56-Positive Multiple Myeloma
Primary Endpoint
This study evaluates dose-limiting toxicity (through cycle 1) and maximum tolerated dose (for the duration of the study).
Other Endpoint
Assessed endpoints include qualitative/quantitative toxicities, pharmacokinetics, and anti-tumor activity (response rate, progression-free survival, overall survival), all measured for the duration of the study.
Experiment 3 Reporting the Activity Date of This ADC [3]
Patients Enrolled
Eligible patients must be ≥18 years, have ECOG ≤2, meet CD56-positive criteria, and have received 1-3 prior regimens (including lenalidomide/bortezomib if applicable). Exclusions include active infections, significant cardiac disease, recent chemotherapy/radiation, neuropathy ≥grade 2, or inadequate organ function (ANC ≥1000, platelets ≥50K, creatinine ≤1.5x ULN). Strict contraception and compliance with RevAssist® are mandated.

   Click to Show/Hide
Administration Dosage
dose escalation study. dosing on days 1, 8 and 15 every 28 days
Related Clinical Trial
NCT Number NCT00991562  Clinical Status PHASE1
Clinical Description
An Open-Label Phase I Study of Bb-10901 (IMGN901, huN901-DM10 in Combination With Lenalidomide and Dexamethasone in Patients With CD56-positive Relapsed or Relapsed/Refractory Multiple Myeloma
Primary Endpoint
The study aims to determine the MTD/RPTD and assess the response rate of the combination therapy in patients with CD56-positive relapsed/refractory multiple myeloma, evaluating efficacy through objective response rate, duration of responses, progression-free survival, and overall survival.
Other Endpoint
Key pharmacodynamic outcomes and safety parameters, including ORR, CR rates, time to progression, and survival metrics, will be monitored throughout the study duration.
Experiment 4 Reporting the Activity Date of This ADC [4]
Patients Enrolled
Eligible patients (age &ge;1, Karnofsky/Lansky &ge;50) must have measurable disease (exceptions: MIBG-avid neuroblastoma), prior standard therapy, and adequate organ function (ANC &ge;750-1000/uL, platelets &ge;75K-100K/uL, GFR &ge;70 mL/min). Exclusions include active CNS metastases, neuropathy &ge;grade 2, uncontrolled infections, recent chemotherapy (<3 weeks), pregnancy, or prior IMGN901 exposure. Reproductive-age participants must use contraception.

   Click to Show/Hide
Administration Dosage
Patients receive lorvotuzumab mertansine IV over 1-1.5 hours on days 1 and 8. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.
Related Clinical Trial
NCT Number NCT02452554  Clinical Status PHASE2
Clinical Description
A Phase 2 Study of IMGN901 (Lorvotuzumab Mertansine; NSC#: 783609) in Children With Relapsed or Refractory Wilms Tumor, Rhabdomyosarcoma, Neuroblastoma, Pleuropulmonary Blastoma, Malignant Peripheral Nerve Sheath Tumor (MPNST) and Synovial Sarcoma
Primary Endpoint
The study evaluates objective response rates (ORR) per RECIST v1.1 in pediatric/adolescent solid tumors (Wilms tumor, rhabdomyosarcoma, neuroblastoma, and other CD56+ malignancies), assessing partial/complete responses over 18 weeks. Toxicity profiles of lorvotuzumab mertansine will be monitored via NCI CTCAE v4.0 for 12 months.
Other Endpoint
Key endpoints focus on response stratification and safety, with Clopper-Pearson confidence intervals for ORR and detailed toxicity summaries by cycle and attribution.
Experiment 5 Reporting the Activity Date of This ADC [5]
Patients Enrolled
Eligible patients were &ge;18 years with untreated extensive-stage SCLC (ECOG 0-2). Exclusion criteria included pregnancy/lactation and prior SCLC chemotherapy. The control arm served primarily for safety validation rather than powered efficacy comparisons.
Administration Dosage
Phase 2 regimen is IMGN901, Carboplatin, and Etoposide. IMGN901 to be given on days 1 and 8 every 21 days.
Related Clinical Trial
NCT Number NCT01237678  Clinical Status PHASE1|||PHASE2
Clinical Description
A Phase 1/2 Study to Assess the Safety and Efficacy of Lorvotuzumab Mertansine in Combination With Carboplatin/Etoposide in Patients With Advanced Solid Tumors Including Extensive Stage Small Cell Lung Cancer
Primary Endpoint
The primary Phase I objective was determining the MTD of IMGN901 in combination with carboplatin/etoposide for solid tumors, with DLTs assessed during Cycle 1 (21 days), including febrile neutropenia, grade ≥3 toxicities, and treatment-delaying events. Phase II focused on PFS in extensive-stage SCLC patients comparing the IMGN901 triplet regimen against historical carboplatin/etoposide controls.

   Click to Show/Hide
Other Endpoint
Safety profiles were evaluated through TEAEs/SAEs (CTCAE v4.0-graded) until 28 days post-treatment. Secondary efficacy metrics included 6-month PFS rates (experimental arm vs historical 44% benchmark) and median OS, though statistical comparisons were limited by study design.
Experiment 6 Reporting the Activity Date of This ADC [6]
Patients Enrolled
Prior therapy restrictions: &le;3 chemotherapy lines (ovarian patients require platinum exposure), no recent radiotherapy/immunotherapy (4-week washout), and anthracycline doses below cardiotoxicity thresholds. Concurrent antineoplastic treatments are prohibited.
Administration Dosage
dose escalation study, dose will vary per cohort. patients will receive an IV infusion once every three weeks.
Related Clinical Trial
NCT Number NCT00346385  Clinical Status PHASE1
Clinical Description
A Phase I, Open-Label, Dose Escalation Study of Daily Dosing With BB-10901
Primary Endpoint
Safety and pharmacokinetic assessments will evaluate toxicity (via prothrombin time tests) and IMGN901 conjugate/antibody levels during Cycle 1 (21 days), while efficacy focuses on tumor response rates and neuroendocrine biomarkers (neuron-specific enolase/NCAM) measured every 2 cycles.
Other Endpoint
Eligible patients (ECOG 0-2, life expectancy ≥3 months) include relapsed/refractory SCLC (1-3 prior regimens), CD56+ neuroendocrine tumors, and select carcinomas (Merkel cell/ovarian). Key exclusions: uncontrolled metastases, significant cardiorespiratory comorbidities, active infections, or pancreatitis risk factors (elevated LFTs/pancreatic enzymes).

   Click to Show/Hide
Experiment 7 Reporting the Activity Date of This ADC [7]
Efficacy Data Objective Response Rate (ORR)
28.30%
Positive CD56 expression (CD56+++/++)
Patients Enrolled
Relapsed and/or Refractory CD-56-positive Multiple Myeloma.
Administration Dosage
40 mg/m2 (up to a maximum of 140 mg) intravenously once every 3 weeks.
Related Clinical Trial
NCT Number NCT00346255  Clinical Status Phase 1
Clinical Description
BB-10901 in treating patients with relapsed and/or refractory multiple myeloma (IMGN901).
Primary Endpoint
Objective response rate=28.30%.
Other Endpoint
Median progression-free survival=26.10 months (95% CI 1-89 weeks).
MLN2704 [Phase 1/2 (discontinued)]
Identified from the Human Clinical Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [8]
Patients Enrolled
The study includes patients with histologically confirmed prostate adenocarcinoma showing progression via physical exam, imaging, or rising PSA despite castrate testosterone levels. Continuous LHRH analog therapy is required if initiated before screening, while prior anti-androgens require progression post-withdrawal. Effective barrier contraception is mandatory.

   Click to Show/Hide
Administration Dosage
Twenty-three patients received MLN2704 at doses of 18 to 343 mg/m2. Eighteen of these patients received ≥ three doses at 4-week intervals.
Related Clinical Trial
NCT Number NCT00052000  Clinical Status PHASE1
Clinical Description
A Phase 1 Single Ascending Dose Trial of MLN2704 (DM1 Conjugated Monoclonal Antibody MLN591) in Subjects With Metastatic Androgen Independent Prostate Cancer
Experiment 2 Reporting the Activity Date of This ADC [9]
Patients Enrolled
Eligible patients require histologically confirmed metastatic prostate adenocarcinoma, age &ge;18 years, disease progression despite castrate testosterone (<50 ng/dL), and continuous LHRH analog therapy unless surgically castrated. Key exclusions include testosterone >50 ng/dL, recent corticosteroids/chemotherapy, CNS metastases, neuropathy >Grade 2, abnormal labs (platelets <100K/mm <sup>3</sup>, ANC <1.5K/mm <sup>3</sup>, Hct <27%), active infections, severe cardiac/respiratory/renal/hepatic conditions, or limited life expectancy (<6 months).

   Click to Show/Hide
Administration Dosage
A total of 62 patients received MLN2704 at ascending doses on 4 schedules: weekly (60, 84, 118, and 165 mg/m2; 12 patients); every 2 weeks (120, 168, 236, and 330 mg/m2; 15 patients); every 3 weeks (330 and 426 mg/m2; 18 patients); and on days 1 and 15 of a 6-week schedule (6-week cycle, 330 mg/m2; 17 patients).
Related Clinical Trial
NCT Number NCT00070837  Clinical Status PHASE1|||PHASE2
Clinical Description
A Phase 1/2 Dose Escalation Trial of Multiple Doses of MLN2704 (DM1 Conjugated Monoclonal Antibody MLN591) in Subjects With Metastatic Androgen-Independent Prostate Cancer
Bivatuzumab mertansine [Phase 1 (discontinued)]
Identified from the Human Clinical Data
Click To Hide/Show 10 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [10]
Patients Enrolled
Eligible patients (18-80 years) must have histologically confirmed recurrent/metastatic head/neck or esophageal squamous cell carcinoma refractory to standard treatments, measurable disease, ECOG &le;2, and life expectancy &ge;3 months. Key exclusions include antibody hypersensitivity, active infections, untreated brain metastases, grade &ge;2 neuropathy, significant hematologic/hepatic/renal dysfunction (ANC <1500/mm <sup>3</sup>, platelets <100K/mm <sup>3</sup>, bilirubin >1.5mg/dl, AST/ALT >3&times;ULN, creatinine >1.5mg/dl), recent anticancer therapy (<4 weeks), pregnancy, or protocol non-compliance.

   Click to Show/Hide
Related Clinical Trial
NCT Number NCT02254044  Clinical Status PHASE1
Clinical Description
An Open Phase I Dose Escalation Study of Bivatuzumab Mertansine Administered Intravenously Once Per Week for Three Weeks in Patients With Advanced Squamous Cell Carcinoma of the Head and Neck or Esophagus With Repeated Administration Courses in Patients With Clinical Benefit
Primary Endpoint
The primary objective is to determine the maximum tolerated dose (MTD) of the investigational drug within a 6-month observation period.
Other Endpoint
Safety evaluations include monitoring adverse events (graded by CTC criteria), clinically significant lab/vital sign abnormalities, and HAHA development for 14 days post-treatment. Pharmacokinetic parameters (AUC0-168, AUC0-tz, AUC0-∞, Cmax, tmax, t1/2, MRT, CL, Vss, Vz, Cpre,ss, Cmin,ss, LI, RA) are assessed for 14 days post-dosing. Tumor response is evaluated per RECIST criteria.

   Click to Show/Hide
Experiment 2 Reporting the Activity Date of This ADC [11]
Patients Enrolled
Eligible patients are women &ge;18 years with CD44v6+ (&ge;50% tumor cells) metastatic breast cancer refractory to anthracyclines/taxanes, measurable lesions (MRI/CT), ECOG &le;2, and life expectancy &ge;6 months. Exclusions include antibody hypersensitivity, active infections, untreated brain metastases, grade &ge;2 neuropathy, hematologic/organ dysfunction (ANC <1500/mm <sup>3</sup>, platelets <100K/mm <sup>3</sup>, bilirubin >1.5mg/dl, AST/ALT >3&times;ULN, creatinine >1.5mg/dl), recent anticancer therapy (<4 weeks), pregnancy, or protocol non-compliance.

   Click to Show/Hide
Related Clinical Trial
NCT Number NCT02254005  Clinical Status PHASE1
Clinical Description
An Open Phase I Single Dose Escalation Study of Bivatuzumab Mertansine Administered Intravenously in Female Patients With CD44v6 Positive Metastatic Breast Cancer With Repeated Administration in Patients With Clinical Benefit
Primary Endpoint
The study aims to determine the maximum tolerated dose (MTD) of bivatuzumab mertansine within a 21-day evaluation period.
Other Endpoint
Safety assessments (AEs, lab abnormalities, vital signs) and pharmacokinetic markers (drug concentration, anti-CD44v6-IgG, HAHA development) are monitored for 21 days. Tumor response is evaluated per RECIST criteria over 1 year.
Experiment 3 Reporting the Activity Date of This ADC [12]
Patients Enrolled
Eligible patients are women &ge;18 years with CD44v6+ (&ge;50% tumor cells) locally recurrent/metastatic breast cancer refractory to anthracyclines/taxanes, having measurable lesions (MRI/CT), ECOG &le;2, and &ge;6 months life expectancy. Key exclusions include antibody hypersensitivity, active infections, untreated brain metastases, grade &ge;2 neuropathy, significant hematologic/organ dysfunction, recent anticancer therapies (<4 weeks), pregnancy/lactation, or protocol non-compliance.

   Click to Show/Hide
Related Clinical Trial
NCT Number NCT02254031  Clinical Status PHASE1
Clinical Description
An Open Phase I Dose Escalation Study of Bivatuzumab Mertansine Administered Intravenously Once Per Week for Three Weeks in Female Patients With CD44v6 Positive Recurrent or Metastatic Breast Cancer With Repeated Administration Courses in Patients With Clinical Benefit
Primary Endpoint
The primary objective is to determine the maximum tolerated dose (MTD) of the study drug, with evaluation up to 6 months from treatment initiation.
Other Endpoint
Secondary outcomes include safety assessments (adverse events graded by CTC criteria, lab abnormalities, vital signs, and HAHA development) and comprehensive pharmacokinetic parameters (AUC, Cmax, tmax, clearance rates, volume of distribution) measured within 14 days post-treatment. Tumor response will be evaluated per RECIST criteria during this same timeframe.

   Click to Show/Hide
Experiment 4 Reporting the Activity Date of This ADC [13]
Patients Enrolled
Enrollment criteria: Adults (&ge;18 years) with histologically confirmed, measurable recurrent/metastatic disease (MRI/CT), ECOG &le;2, &ge;6-month life expectancy, and no active infections/brain metastases. Excluded: hypersensitivity to immunoconjugates, significant cytopenias/organ dysfunction, recent anticancer therapies (<3-4 weeks), pregnancy, or protocol non-adherence.

   Click to Show/Hide
Related Clinical Trial
NCT Number NCT02254018  Clinical Status PHASE1
Clinical Description
An Open Phase I Single Dose Escalation Study of Bivatuzumab Mertansine Administered Intravenously in Patients With Advanced Squamous Cell Carcinoma of the Head and Neck With Repeated Administration in Patients With Clinical Benefit
Primary Endpoint
The primary endpoint is determining the maximum tolerated dose (MTD) of bivatuzumab mertansine within a 21-day evaluation period in patients with treatment-refractory head and neck squamous cell carcinoma.
Other Endpoint
Secondary assessments include safety profiles (CTC-graded adverse events, lab/vital sign abnormalities, HAHA development) and efficacy (RECIST tumor response monitored for 1 year), along with pharmacokinetic measurements (drug and anti-CD44v6-IgG concentrations) during the 21-day treatment course.
Experiment 5 Reporting the Activity Date of This ADC [14]
Efficacy Data Objective Response Rate (ORR)
0%
Patients Enrolled
Metastatic breast cancer (MBC) that expresses CD44v6 in at least 50% of tumor cells in primary tumor tissue as assessed by immunohistochemistry, pretreatment with anthracyclines and taxanes, tumor metastases measurable by computed tomography (CT) or magnetic resonance imaging (MRI), life expectancy of at least 6 months, no chemotherapy, radiotherapy or immunotherapy within the last 4 weeks before study entry, adequate organ function, Eastern Cooperative Oncology Group performance score 2.

   Click to Show/Hide
Administration Dosage
One single intravenous infusion over 30 min, dose was escalated in 25 mg/m2 increments up to the maximum tolerated dose (MTD).
Related Clinical Trial
NCT Number NCT02254005  Clinical Status Phase 1
Clinical Description
An open phase 1 single dose escalation study of bivatuzumab mertansine administered intravenously in female patients with CD44v6 positive metastatic breast cancer with repeated administration in patients with clinical benefit.
Primary Endpoint
The MTD in this trial could not be determined.
Other Endpoint
No objective responses were observed. Disease stabilization was achieved in 50.00% of patients independently of dose level.
Experiment 6 Reporting the Activity Date of This ADC [16]
Patients Enrolled
Ecurrent or metastatic head and neck squamous cell carcinoma (HNSCC) not amenable to established treatments, an ECOG score 2, and an estimated life expectancy of at least 6 months, a tumor diameter of at least 1 cm in CT or MRI scans was also required.
Administration Dosage
Starting with 25 mg/m2, the dose was escalated in steps of 25 mg/m2 until dose limiting toxicity was observed, intravenously.
Related Clinical Trial
NCT Number NCT02254044  Clinical Status Phase 1
Clinical Description
An open phase 1 dose escalation study of bivatuzumab mertansine administered intravenously once per week for three weeks in patients with advanced squamous cell carcinoma of the head and neck or esophagus with repeated administration courses in patients with clinical benefit.
Primary Endpoint
The MTD was 300 mg/m2.
Other Endpoint
Due to the premature discontinuation of the trial efficacy complying with the study plan could not be assessed. In 3 patients,a partial response at doses of 2.00, 2.75 and 3.25 mg/m2.
Experiment 7 Reporting the Activity Date of This ADC [17]
Related Clinical Trial
NCT Number NCT02254044  Clinical Status Phase 1
Clinical Description
An open phase 1 dose escalation study of bivatuzumab mertansine administered intravenously once per week for three weeks in patients with advanced squamous cell carcinoma of the head and neck or esophagus with repeated administration courses in patients with clinical benefit.
Experiment 8 Reporting the Activity Date of This ADC [18]
Related Clinical Trial
NCT Number NCT02254031  Clinical Status Phase 1
Clinical Description
An open phase 1 dose escalation study of bivatuzumab mertansine administered intravenously once per week for three weeks in female patients with CD44V6 positive recurrent or metastatic breast cancer with repeated administration courses in patients with clinical.
Experiment 9 Reporting the Activity Date of This ADC [19]
Related Clinical Trial
NCT Number NCT02254005  Clinical Status Phase 1
Clinical Description
An open phase 1 single dose escalation study of bivatuzumab mertansine administered intravenously in female patients with CD44v6 positive metastatic breast cancer with repeated administration in patients with clinical benefit.
Experiment 10 Reporting the Activity Date of This ADC [20]
Related Clinical Trial
NCT Number NCT02254018  Clinical Status Phase 1
Clinical Description
An open phase 1 single dose escalation study of bivatuzumab mertansine administered intravenously in patients with advanced squamous cell carcinoma of the head and neck with repeated administration in patients with clinical benefit.
Cantuzumab mertansine [Phase 1 (discontinued)]
Identified from the Human Clinical Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [15]
Efficacy Data Objective Response Rate (ORR)
0%
Patients Enrolled
Histological documentation of advanced or metastatic epithelial solid tumor which were likely to express the CanAg antigen, that were refractory or resistant to standard chemotherapy, or for which no effective standard therapy exists.
Administration Dosage
IV infusion at an initial dose of 30 mg/m2, three times per week for three consecutive weeks for a total of nine doses.
Experiment 2 Reporting the Activity Date of This ADC [21]
Patients Enrolled
Solid malignancies refractory to standard therapy or for whom no standard therapy existed.
Administration Dosage
IV cantuzumab mertansine was administered at a rate of 1 mg/min for 30 minutes and then increased to 3 mg/min if hypersensitivity phenomena were not observed. Treatment courses were repeated every 3 weeks.
F105-SPP-DM1 [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 [22]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 17.58% Positive ITGAV expression (ITGAV +++/++)
Method Description
The rear flank region of female athymic rats were implanted with 5x106 cells subcutaneously (0.2 ml of25 x106 cells/ml) on the rear flank area. When mean tumor volumes reached to 250 mm3, dosed intravenously (15 mg/kg) on days 17 and 29 after tumor cell injection.
In Vivo Model A549 CDX model
In Vitro Model Lung adenocarcinoma A-549 cells CVCL_0023
Experiment 2 Reporting the Activity Date of This ADC [22]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 20.88% Positive ITGAV expression (ITGAV +++/++)
Method Description
Female athymic rats were inoculated with 5x106 HT29 cells subcutancously on the rear flank area. The animals were stratified into 13 groups, 6 animals per group based on a mean tumor volume for each group of approximately 250 mm3. On the day of grouping (day 7) each group received its initial dosing (175 ug/kg).
In Vivo Model HT-29 CDX model
In Vitro Model Colon cancer HT29 cells CVCL_A8EZ
CNTO95-SPP-DM1 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 8 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [22]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 28.74% Positive ITGAV expression (ITGAV +++/++)
Method Description
On the day of grouping (Day 0), animals were weighed and intravenously injectedwith control ADC at 25 mg/kg. All testand control articles were given in a volume of 1ml/100 gm of body weight. CNTO 364 at 3 mg/kg groups was administered i.v. on a q7dx5 schedule.
In Vivo Model A375.S2 CDX model
In Vitro Model Amelanotic melanoma A375.S2 cells CVCL_0136
Experiment 2 Reporting the Activity Date of This ADC [22]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 44.54% Positive ITGAV expression (ITGAV +++/++)
Method Description
On the day of grouping (Day 0), animals were weighed and intravenously injectedwith control ADC at 25 mg/kg. All testand control articles were given in a volume of 1ml/100 gm of body weight. CNTO 364 at 6 mg/kg groups was administered i.v. on a q7dx5 schedule.
In Vivo Model A375.S2 CDX model
In Vitro Model Amelanotic melanoma A375.S2 cells CVCL_0136
Experiment 3 Reporting the Activity Date of This ADC [22]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 45.81% Positive ITGAV expression (ITGAV +++/++)
Method Description
Female athymic rats were inoculated with 5x106 HT29 cells subcutancously on the rear flank area. The animals were stratified into 13 groups, 6 animals per group based on a mean tumor volume for each group of approximately 250 mm3. On the day of grouping (day 7) each group received its initial dosing (175 ug/kg).
In Vivo Model HT-29 CDX model
In Vitro Model Colon cancer HT29 cells CVCL_A8EZ
Experiment 4 Reporting the Activity Date of This ADC [22]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 71.21% Positive ITGAV expression (ITGAV +++/++)
Method Description
Nine-week-old athymic nude rats were subcutaneously inoculated with A375.S2human melanoma cells. ADC (5 mg/kg) andappropriate control compounds were intravenously injected (three injection every other day inthe first week followed by one injection per week for two weeks.
In Vivo Model A375.S2 CDX model
In Vitro Model Amelanotic melanoma A375.S2 cells CVCL_0136
Experiment 5 Reporting the Activity Date of This ADC [22]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 77.15% Positive ITGAV expression (ITGAV +++/++)
Method Description
Nine-week-old athymic nude rats were subcutaneously inoculated with A375.S2human melanoma cells. ADC (10 mg/kg) andappropriate control compounds were intravenously injected (three injection every other day inthe first week followed by one injection per week for two weeks.
In Vivo Model A375.S2 CDX model
In Vitro Model Amelanotic melanoma A375.S2 cells CVCL_0136
Experiment 6 Reporting the Activity Date of This ADC [22]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 87.23% Positive ITGAV expression (ITGAV +++/++)
Method Description
On the day of grouping (Day 0), animals were weighed and intravenously injectedwith control ADC at 25 mg/kg. All testand control articles were given in a volume of 1ml/100 gm of body weight. CNTO 364 at 10 mg/kg groups was administered i.v. on a q7dx5 schedule.
In Vivo Model A375.S2 CDX model
In Vitro Model Amelanotic melanoma A375.S2 cells CVCL_0136
Experiment 7 Reporting the Activity Date of This ADC [22]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 95.10% Positive ITGAV expression (ITGAV +++/++)
Method Description
The rear flank region of female athymic rats were implanted with 5x106 cells subcutaneously (0.2 ml of25 x106 cells/ml) on the rear flank area. When mean tumor volumes reached to 250 mm3, dosed intravenously (15 mg/kg) on days 17 and 29 after tumor cell injection.
In Vivo Model A549 CDX model
In Vitro Model Lung adenocarcinoma A-549 cells CVCL_0023
Experiment 8 Reporting the Activity Date of This ADC [22]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 95.81% Positive ITGAV expression (ITGAV +++/++)
Method Description
On the day of grouping (Day 0), animals were weighed and intravenously injectedwith control ADC at 25 mg/kg. All testand control articles were given in a volume of 1ml/100 gm of body weight. CNTO 364 at 15 mg/kg groups was administered i.v. on a q7dx5 schedule.
In Vivo Model A375.S2 CDX model
In Vitro Model Amelanotic melanoma A375.S2 cells CVCL_0136
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 [22]
Efficacy Data Half Maximal Effective Concentration (EC50)
1 ug/mL
Positive ITGAV expression (ITGAV +++/++)
Method Description
Cells were seeded into white 96-well tissue culture plates (5000 cells/well)in culture medium and incubated for 16 hrs. Serial dilutions of immunoconjugates were added toeach appropraite wells (0-20 ug/ml). Tissue culture plates were incubated at 37°C for 96 hrs.
In Vitro Model Colon cancer HT29 cells CVCL_A8EZ
Experiment 2 Reporting the Activity Date of This ADC [22]
Efficacy Data Half Maximal Effective Concentration (EC50)
1.2 ug/mL
Positive ITGAV expression (ITGAV +++/++)
Method Description
Cells were seeded into white 96-well tissue culture plates (5000 cells/well)in culture medium and incubated for 16 hrs. Serial dilutions of immunoconjugates were added toeach appropraite wells (0-20 ug/ml). Tissue culture plates were incubated at 37°C for 96 hrs.
In Vitro Model Lung adenocarcinoma A-549 cells CVCL_0023
Experiment 3 Reporting the Activity Date of This ADC [22]
Efficacy Data Half Maximal Effective Concentration (EC50)
0.19 mg/mL
Positive ITGAV expression (ITGAV +++/++)
Method Description
Cells were harvested, rinsedsuspended in serum free DMEM, and sequentially incubated for 60 minutes on ice with serialdiluted CNTO 95,CNTO 364, CNTO 365 and CNTO 366 and FITC-labeled anti-humanantibody (10 mg/ml).
In Vitro Model Colon cancer HT29 cells CVCL_A8EZ
Experiment 4 Reporting the Activity Date of This ADC [22]
Efficacy Data Half Maximal Effective Concentration (EC50)
0.27 mg/mL
Positive ITGAV expression (ITGAV +++/++)
Method Description
Cells were harvested, rinsedsuspended in serum free DMEM, and sequentially incubated for 60 minutes on ice with serialdiluted CNTO 95,CNTO 364, CNTO 365 and CNTO 366 and FITC-labeled anti-humanantibody (10 mg/ml).
In Vitro Model Ovarian endometrioid adenocarcinoma A2780 cells CVCL_0134
Experiment 5 Reporting the Activity Date of This ADC [22]
Efficacy Data Half Maximal Effective Concentration (EC50)
0.27 mg/mL
Positive ITGAV expression (ITGAV +++/++)
Method Description
Cells were harvested, rinsedsuspended in serum free DMEM, and sequentially incubated for 60 minutes on ice with serialdiluted CNTO 95,CNTO 364, CNTO 365 and CNTO 366 and FITC-labeled anti-humanantibody (10 mg/ml).
In Vitro Model Lung adenocarcinoma A-549 cells CVCL_0023
Mirvetuximab-SPP-DM1 [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 [23]
Efficacy Data Tumor Growth Inhibition value (TGI)
32.17%
High FOLR1 expression (FOLR1+++; 4,500,000 FOLR1 molecules/cell)
Method Description
Animals with established tumors of about 130 mm3 were treated with intravenous single injection of the M9346A-DM conjugates at 25 02 mg/kg, equivalent to 51 3 g conjugated maytansinoid per kg The conjugates were injected on day 20 after cell inoculation.
In Vivo Model FRalpha-positive KB CDX model
In Vitro Model Human papillomavirus-related endocervical adenocarcinoma KB cells CVCL_0372
Experiment 2 Reporting the Activity Date of This ADC [23]
Efficacy Data Tumor Growth Inhibition value (TGI)
50%
High FOLR1 expression (FOLR1+++; 1,300,000 FOLR1 molecules/cell)
Method Description
Animals with established tumors of about 130 mm3 were treated with intravenous single injection of the M9346A-DM conjugates at 25 02 mg/kg, equivalent to 51 3 g conjugated maytansinoid per kg The conjugates were injected on day 7 after cell inoculation.
In Vivo Model Ovarian carcinoma Igrov-1 CDX model
In Vitro Model Ovarian endometrioid adenocarcinoma IGROV-1 cells CVCL_1304
Revealed Based on the Cell Line Data
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [23]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.11±0.04 nM
High FOLR1 expression (FOLR1+++; 4,500,000 FOLR1 molecules/cell)
Method Description
Dilutions of conjugates or unconjugated maytansinoid in the appropriate culture medium were added to wells of 96-well flat-bottomed plates containing 1 x103 cells per well The plates were incubated at 37°C, 6% CO2 for either 5 days (continuos exposure) or for 4 hours followed by 5-day incubation in conjugate-free medium (short exposure). Cell viability was determined by the WST-8 assay in accordance with the manufacturer's protocol, and IC50 were generated using a sigmoidal dose-response (variable slope) nonlinear regression curve fit.

   Click to Show/Hide
In Vitro Model Human papillomavirus-related endocervical adenocarcinoma KB cells CVCL_0372
Experiment 2 Reporting the Activity Date of This ADC [23]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.13±0.08 nM
Moderate FOLR1 expression (FOLR1++; 290,000 FOLR1 molecules/cell)
Method Description
Dilutions of conjugates or unconjugated maytansinoid in the appropriate culture medium were added to wells of 96-well flat-bottomed plates containing 1 x103 cells per well The plates were incubated at 37°C, 6% CO2 for either 5 days (continuos exposure) or for 4 hours followed by 5-day incubation in conjugate-free medium (short exposure). Cell viability was determined by the WST-8 assay in accordance with the manufacturer's protocol, and IC50 were generated using a sigmoidal dose-response (variable slope) nonlinear regression curve fit.

   Click to Show/Hide
In Vitro Model Gestational choriocarcinoma JEG-3 cells CVCL_0363
Experiment 3 Reporting the Activity Date of This ADC [23]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.14±0.05 nM
High FOLR1 expression (FOLR1+++; 1,300,000 FOLR1 molecules/cell)
Method Description
Dilutions of conjugates or unconjugated maytansinoid in the appropriate culture medium were added to wells of 96-well flat-bottomed plates containing 1 x103 cells per well The plates were incubated at 37°C, 6% CO2 for either 5 days (continuos exposure) or for 4 hours followed by 5-day incubation in conjugate-free medium (short exposure). Cell viability was determined by the WST-8 assay in accordance with the manufacturer's protocol, and IC50 were generated using a sigmoidal dose-response (variable slope) nonlinear regression curve fit.

   Click to Show/Hide
In Vitro Model Ovarian endometrioid adenocarcinoma IGROV-1 cells CVCL_1304
Anti-KIT NEG085-SPP-DM1 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [24]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 41.55% Positive KIT expression (KIT+++/++)
Method Description
Female SCID-beige mice were implanted subcutaneously with 10,000,000 NCI-H1048 cells. The total injection volume containingcells in suspension was 200 ul. Mice were enrolled in the study 15 days post implantation withaverage tumor volume of about 120 mm3. All treated groups received a single intravenous dose of 2 mg/kg. After being randomly assigned to groups (n = 8/group), mice were administered a single i.v.dose of TBS (5 ml/kg) or ADC (2.5 mg/kg).

   Click to Show/Hide
In Vivo Model NCI-H1048 CDX model
In Vitro Model Lung small cell carcinoma NCI-H1048 cells CVCL_1453
Experiment 2 Reporting the Activity Date of This ADC [24]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 87.55% Positive KIT expression (KIT+++/++)
Method Description
Female SCID-beige mice were implanted subcutaneously with 10,000,000 NCI-H1048 cells. The total injection volume containingcells in suspension was 200 ul. Mice were enrolled in the study 15 days post implantation withaverage tumor volume of about 120 mm3. All treated groups received a single intravenous dose of 2 mg/kg. After being randomly assigned to groups (n = 8/group), mice were administered a single i.v.dose of TBS (5 ml/kg) or ADC (5 mg/kg).

   Click to Show/Hide
In Vivo Model NCI-H1048 CDX model
In Vitro Model Lung small cell carcinoma NCI-H1048 cells CVCL_1453
Experiment 3 Reporting the Activity Date of This ADC [24]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 91.32% Positive KIT expression (KIT+++/++)
Method Description
Female SCID-beige mice were implanted subcutaneously with 10,000,000 NCI-H1048 cells. The total injection volume containingcells in suspension was 200 ul. Mice were enrolled in the study 15 days post implantation withaverage tumor volume of about 120 mm3. All treated groups received a single intravenous dose of 2 mg/kg. After being randomly assigned to groups (n = 8/group), mice were administered a single i.v.dose of TBS (5 ml/kg) or ADC (10 mg/kg).

   Click to Show/Hide
In Vivo Model NCI-H1048 CDX model
In Vitro Model Lung small cell carcinoma NCI-H1048 cells CVCL_1453
B4-SPP-DC44 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [25]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 64% Positive CD19 expression (CD19+++/++)
Method Description
Animals with established subcutaneous xenograft Ramos tumors were treated with either huB4-SPP-DC4 (DC4 dose of 75 ug/kg, qdx5), or huB4-SPP-DC44 (DC44 dose of 75 ug/kg, qdx5), unconjugated DC4 (75 ug/kg, qdx5), unconjugated DC44 (75 ug/kg, qdx5), or with phosphate-buffered saline vehicle (control), administered intravenously, and the tumor growth was monitored.

   Click to Show/Hide
In Vivo Model Ramos CDX model
In Vitro Model Burkitt lymphoma Ramos cells CVCL_0597
Revealed Based on the Cell Line Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [25]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.4 nM
Positive CD19 expression (CD19+++/++)
Method Description
Cytotoxicity of B4-SPP-DCx Conjugates (with acid phosphatase treatment) against Ramos (Ag+) and HL60/s (Ag-) Cells.
In Vitro Model Burkitt lymphoma Ramos cells CVCL_0597
Experiment 2 Reporting the Activity Date of This ADC [25]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 1.8 nM Negative CD19 expression(CD19-)
Method Description
Cytotoxicity of B4-SPP-DCx Conjugates (with acid phosphatase treatment) against Ramos (Ag+) and HL60/s (Ag-) Cells.
In Vitro Model Adult acute myeloid leukemia HL-60 cells CVCL_0002
B-B4-SPP-DM1 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [26]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 77.45% Positive CD138 expression (CD138 +++/++)
Method Description
MOLP-8 cells (1.5x107 cells per mouse) suspended in a 50:50 mixture of serum free media and matrigel were injected subcutaneously in the area under the right shoulder in 100 ul. Nine groups (n=6) were treated with a single intravenous injection of ADCs, each at doses of 250 ug/kg.
In Vivo Model MOLP-8 CDX model
In Vitro Model Plasma cell myeloma MOLP-8 cells CVCL_2124
Tmab-SPP-DM1 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [27]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 77.60% High HER2 expression (HER2+++)
Method Description
Mice bearing mammary tumor transplants from the MMTV-HER2 Fo5 line were given a single iv injection (10 mg/kg) of Tmab-SPP-DM1, Tmab-SSNPP-DM3, Tmab-SSNPP-DM4, Tmab-MCC-DM1, or vehicle (n=7 mice per group), and tumor growth was monitored for 25 days.
In Vivo Model MMTV-HER2 Fo5 CDX model (Trastuzumab resistant)
In Vitro Model Breast cancer MMTV-HER2 cells Mus musculus
Revealed Based on the Cell Line Data
Click To Hide/Show 4 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [27]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.22 nM
High HER2 expression (HER2+++)
Method Description
The effects of trastuzumab and trastuzumab-maytansinoid conjugates on tumor cell viability were assessed using Cell Titer-Glo. Cells were plated in black-walled 96-well plates (20,000 per well for BT-474; 10,000 cells per well for all other lines) and allowed to adhere overnight at 37°C in a humidified atmosphere of 5% CO2. For measurement of apoptosis, BT-474 and SK-BR-3 were exposed to trastuzumab or trastuzumab-DM for 48 h.

   Click to Show/Hide
In Vitro Model Breast adenocarcinoma SK-BR-3 cells CVCL_0033
Experiment 2 Reporting the Activity Date of This ADC [27]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
4.26 nM
High HER2 expression (HER2+++)
Method Description
The effects of trastuzumab and trastuzumab-maytansinoid conjugates on tumor cell viability were assessed using Cell Titer-Glo. Cells were plated in black-walled 96-well plates (20,000 per well for BT-474; 10,000 cells per well for all other lines) and allowed to adhere overnight at 37°C in a humidified atmosphere of 5% CO2. For measurement of apoptosis, BT-474 and SK-BR-3 were exposed to trastuzumab or trastuzumab-DM for 48 h.

   Click to Show/Hide
In Vitro Model Invasive breast carcinoma BT-474 cells CVCL_0179
Experiment 3 Reporting the Activity Date of This ADC [27]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
41.37 nM
Negative HER2 expression (HER2-)
Method Description
The effects of trastuzumab and trastuzumab-maytansinoid conjugates on tumor cell viability were assessed using Cell Titer-Glo. Cells were plated in black-walled 96-well plates (20,000 per well for BT-474; 10,000 cells per well for all other lines) and allowed to adhere overnight at 37°C in a humidified atmosphere of 5% CO2. Medium was then removed and replaced by fresh culture medium containing different concentrations of trastuzumab, trastuzumab ADC, or free DM1, and the cells incubated for varying periods of time.

   Click to Show/Hide
In Vitro Model Breast adenocarcinoma MDA-MB-468 cells CVCL_0419
Experiment 4 Reporting the Activity Date of This ADC [27]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 100 nM Low HER2 expression (HER2+)
Method Description
The effects of trastuzumab and trastuzumab-maytansinoid conjugates on tumor cell viability were assessed using Cell Titer-Glo. Cells were plated in black-walled 96-well plates (20,000 per well for BT-474; 10,000 cells per well for all other lines) and allowed to adhere overnight at 37°C in a humidified atmosphere of 5% CO2. Medium was then removed and replaced by fresh culture medium containing different concentrations of trastuzumab, trastuzumab ADC, or free DM1, and the cells incubated for varying periods of time.

   Click to Show/Hide
In Vitro Model Invasive breast carcinoma MCF-7 cells CVCL_0031
NBT062-SPP-DM1 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [26]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 77.61% Positive CD138 expression (CD138 +++/++)
Method Description
MOLP-8 cells (1.5x107 cells per mouse) suspended in a 50:50 mixture of serum free media and matrigel were injected subcutaneously in the area under the right shoulder in 100 ul. Nine groups (n=6) were treated with a single intravenous injection of ADCs, each at doses of 250 ug/kg.
In Vivo Model MOLP-8 CDX model
In Vitro Model Plasma cell myeloma MOLP-8 cells CVCL_2124
Experiment 2 Reporting the Activity Date of This ADC [26]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 84.27% Positive CD138 expression (CD138 +++/++)
Method Description
MOLP-8 cells (1.5x107 cells per mouse) suspended in a 50:50 mixture of serum free media and matrigel were injected subcutaneously in the area under the right shoulder in 100 ul. Nine groups (n=6) were treated with a single intravenous injection of ADCs, each at doses of 250 ug/kg.
In Vivo Model MOLP-8 CDX model
In Vitro Model Plasma cell myeloma MOLP-8 cells CVCL_2124
Experiment 3 Reporting the Activity Date of This ADC [26]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 92.11% Positive CD138 expression (CD138 +++/++)
Method Description
MOLP-8 cells (1.5x107 cells per mouse) suspended in a 50:50 mixture of serum free media and matrigel were injected subcutaneously in the area under the right shoulder in 100 ul. Nine groups (n=6) were treated with a single intravenous injection of ADCs, each at doses of 450 ug/kg.
In Vivo Model MOLP-8 CDX model
In Vitro Model Plasma cell myeloma MOLP-8 cells CVCL_2124
Revealed Based on the Cell Line Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [26]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.00-10.00 nM
Positive CD138 expression (CD138 +++/++)
Method Description
CD138+ MOLP-8 cells were seeded in flat bottom plates at 3000 cells/well. CD138- BJAB control cells were seeded at 1000 cells/weli. The cells were treated with nBT062-SPDB-DM4nBT062-SPP-DM1 or nBT062-SMCC-DM1 at different concentrations for five days.
In Vitro Model Plasma cell myeloma MOLP-8 cells CVCL_2124
Experiment 2 Reporting the Activity Date of This ADC [26]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 100 nM Negative CD138 expression (CD138 -)
Method Description
CD138+ MOLP-8 cells were seeded in flat bottom plates at 3000 cells/well. CD138- BJAB control cells were seeded at 1000 cells/weli. The cells were treated with nBT062-SPDB-DM4nBT062-SPP-DM1 or nBT062-SMCC-DM1 at different concentrations for five days.
In Vitro Model Burkitt lymphoma BJAB cells CVCL_5711
B4-SPP-DC4 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [25]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 84% Positive CD19 expression (CD19+++/++)
Method Description
Animals with established subcutaneous xenograft Ramos tumors were treated with either huB4-SPP-DC4 (DC4 dose of 75 ug/kg, qdx5), or huB4-SPP-DC44 (DC44 dose of 75 ug/kg, qdx5), unconjugated DC4 (75 ug/kg, qdx5), unconjugated DC44 (75 ug/kg, qdx5), or with phosphate-buffered saline vehicle (control), administered intravenously, and the tumor growth was monitored.

   Click to Show/Hide
In Vivo Model Ramos CDX model
In Vitro Model Burkitt lymphoma Ramos cells CVCL_0597
Revealed Based on the Cell Line Data
Click To Hide/Show 4 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [25]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
11 pM
Positive CD19 expression (CD19+++/++)
Method Description
Cytotoxicity of B4-SPP-DCx Conjugates (without acid phosphatase treatment) against Ramos (Ag+) and HL60/s (Ag-) Cells.
In Vitro Model Burkitt lymphoma Ramos cells CVCL_0597
Experiment 2 Reporting the Activity Date of This ADC [25]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.74 nM
Positive CD19 expression (CD19+++/++)
Method Description
Cytotoxicity of B4-SPP-DCx Conjugates (with acid phosphatase treatment) against Ramos (Ag+) and HL60/s (Ag-) Cells.
In Vitro Model Burkitt lymphoma Ramos cells CVCL_0597
Experiment 3 Reporting the Activity Date of This ADC [25]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 1.5 nM Negative CD19 expression(CD19-)
Method Description
Cytotoxicity of B4-SPP-DCx Conjugates (with acid phosphatase treatment) against Ramos (Ag+) and HL60/s (Ag-) Cells.
In Vitro Model Adult acute myeloid leukemia HL-60 cells CVCL_0002
Experiment 4 Reporting the Activity Date of This ADC [25]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 3 nM Negative CD19 expression(CD19-)
Method Description
Cytotoxicity of B4-SPP-DCx Conjugates (without acid phosphatase treatment) against Ramos (Ag+) and HL60/s (Ag-) Cells.
In Vitro Model Adult acute myeloid leukemia HL-60 cells CVCL_0002
HuMov19-SPP-DM1 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 5 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [28]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 90.72% Positive FOLR1 expression (FOLR1 +++/++)
Method Description
Conjugates of the exemplary anti-FOLR1 antibodies were tested using an established xenograft model of KB cells implanted subcutaneous into SCID mice. Mice were randomized by body weight into treatment groups and treated once on day 6 post cell inoculation with 2.5 mg/kg of one of the conjugates listed above or with PBS only.
In Vivo Model KB CDX model
In Vitro Model Human papillomavirus-related endocervical adenocarcinoma KB cells CVCL_0372
Experiment 2 Reporting the Activity Date of This ADC [28]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 94.09% Positive FOLR1 expression (FOLR1 +++/++)
Method Description
Conjugates of the exemplary anti-FOLR1 antibodies were tested using an established xenograft model of KB cells implanted subcutaneous into SCID mice. Mice were randomized by body weight into treatment groups and treated once on day 6 post cell inoculation with 5 mg/kg of one of the conjugates listed above or with PBS only.
In Vivo Model KB CDX model
In Vitro Model Human papillomavirus-related endocervical adenocarcinoma KB cells CVCL_0372
Experiment 3 Reporting the Activity Date of This ADC [28]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.1 nM
Positive FOLR1 expression (FOLR1 +++/++)
Method Description
Conjugate in various concentrations was added to FOLR1-expressing cells in a 96 well plate at 1,000 cells per well in 100 pL in complete RPMI medium.
In Vitro Model Ovarian endometrioid adenocarcinoma IGROV-1 cells CVCL_1304
Experiment 4 Reporting the Activity Date of This ADC [28]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.1 nM
Positive FOLR1 expression (FOLR1 +++/++)
Method Description
Conjugate in various concentrations was added to FOLR1-expressing cells in a 96 well plate at 1,000 cells per well in 100 pL in complete RPMI medium.
In Vitro Model Human papillomavirus-related endocervical adenocarcinoma KB cells CVCL_0372
Experiment 5 Reporting the Activity Date of This ADC [28]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.2 nM
Moderate FOLR1 expression (FOLR1 ++)
Method Description
Conjugate in various concentrations was added to FOLR1-expressing cells in a 96 well plate at 1,000 cells per well in 100 pL in complete RPMI medium.
In Vitro Model Gestational choriocarcinoma JEG-3 cells CVCL_0363
M9346A-SPP-DM1 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [28]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 90.98% Positive FOLR1 expression (FOLR1 +++/++)
Method Description
Conjugates of the exemplary anti-FOLR1 antibodies were tested using an established xenograft model of OVCAR-3 cells implanted subcutaneous into SCID mice. Mice were randomized by body weight into treatment groups and treated once post cell inoculation with 5 mg/kg of one of the conjugates listed above or with PBS only.
In Vivo Model OVCAR-3 CDX model
In Vitro Model Ovarian serous adenocarcinoma OVCAR-3 cells CVCL_0465
MuDS6-DM1 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 6 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [29]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 94.50% Positive CA6 expression (CA6 +++/++)
Method Description
To demonstrate the in vivo activity of the muDS6-DM1 conjugate,human tumor xenografts were established in SCID mice.A subcutaneous model of the human pancreatic cancer cell-line HPAC was developed. The dose was 27.7 mg/kg qw x2.
In Vivo Model HPAC CDX model
In Vitro Model Pancreatic adenocarcinoma HPAC cells CVCL_3517
Experiment 2 Reporting the Activity Date of This ADC [29]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100% Positive CA6 expression (CA6 +++/++)
Method Description
To demonstrate the in vivo activity of the muDS6-DM1 conjugate,human tumor xenografts were established in SCID mice.A subcutaneous model of the human cervical cancer cell-line HeLa was developed. The dose was 27.7 mg/kg qw x2.
In Vivo Model HeLa CDX model
In Vitro Model Endocervical adenocarcinoma HeLa cells CVCL_0030
Experiment 3 Reporting the Activity Date of This ADC [29]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100% Positive CA6 expression (CA6 +++/++)
Method Description
To demonstrate the in vivo activity of the muDS6-DM1 conjugate,human tumor xenografts were established in SCID mice.A subcutaneous model of the human ovarian cancer cell-line TOV-21G was developed. The dose was 27.7 mg/kg qw x2.
In Vivo Model TOV-21G CDX model
In Vitro Model Ovarian clear cell adenocarcinoma TOV-21G cells CVCL_3613
Experiment 4 Reporting the Activity Date of This ADC [29]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100% Positive CA6 expression (CA6 +++/++)
Method Description
To demonstrate the in vivo activity of the muDS6-DM1 conjugate,human tumor xenografts were established inSCID mice.A subcutaneous model of the human cervicalcarcinoma cell-line KB was developed. The dose was 27.7 mg/kg qw x2.
In Vivo Model OVCAR-5 CDX model
In Vitro Model Ovarian serous adenocarcinoma OVCAR-5 cells CVCL_1628
Experiment 5 Reporting the Activity Date of This ADC [29]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100% Positive CA6 expression (CA6 +++/++)
Method Description
To demonstrate the in vivo activity of the muDS6-DM1 conjugate,human tumor xenografts were established inSCID mice.A subcutaneous model of the human cervicalcarcinoma cell-line KB was developed. The dose was 250 ug/kg every day for 5 days.
In Vivo Model KB CDX model
In Vitro Model Human papillomavirus-related endocervical adenocarcinoma KB cells CVCL_0372
Experiment 6 Reporting the Activity Date of This ADC [29]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100% Positive CA6 expression (CA6 +++/++)
Method Description
To demonstrate the in vivo activity of the muDS6-DM1 conjugate,human tumor xenografts were established inSCID mice.A subcutaneous model of the human cervicalcarcinoma cell-line KB was developed. The dose was 150 ug/kg every day for 5 days.
In Vivo Model KB CDX model
In Vitro Model Human papillomavirus-related endocervical adenocarcinoma KB cells CVCL_0372
Revealed Based on the Cell Line Data
Click To Hide/Show 28 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [29]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.1 nM
Positive CA6 expression (CA6 +++/++)
Method Description
Clonogenic assays were conducted where cells (1000-2500 cells/well) were plated on6-well plates in 2 ml of conjugate diluted in culture media.The cells were continuously exposed to the conjugate at concentrations,generally between 3x10-11M toseveral 3x10-9 M,and were incubated in a 37°C,6% CO2, humidified chamber for 5-9 days.

   Click to Show/Hide
In Vitro Model Ductal carcinoma BT-483 cells CVCL_2319
Experiment 2 Reporting the Activity Date of This ADC [29]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.45 nM
Positive CA6 expression (CA6 +++/++)
Method Description
In the MTT assay, cells were seeded in 96-well plates ata density of 1000-5000 cells/well. The cells were plated with serial dilutions of either naked muDS6 or muDS6-DM1 immunoconjugate in 200 pl of culture media. The cells and antibody/conjugate mixtures were then incubated for 2-7 d, at which time cellviability was assessed by an MTT assay.
In Vitro Model Invasive breast carcinoma ZR-75-1 cells CVCL_0588
Experiment 3 Reporting the Activity Date of This ADC [29]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.46 nM
Positive CA6 expression (CA6 +++/++)
Method Description
Clonogenic assays were conducted where cells (1000-2500 cells/well) were plated on6-well plates in 2 ml of conjugate diluted in culture media.The cells were continuously exposed to the conjugate at concentrations,generally between 3x10-11M toseveral 3x10-9 M,and were incubated in a 37°C,6% CO2, humidified chamber for 5-9 days.

   Click to Show/Hide
In Vitro Model Endocervical adenocarcinoma WISH cells CVCL_1909
Experiment 4 Reporting the Activity Date of This ADC [29]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.67 nM
Positive CA6 expression (CA6 +++/++)
Method Description
In the MTT assay, cells were seeded in 96-well plates ata density of 1000-5000 cells/well. The cells were plated with serial dilutions of either naked muDS6 or muDS6-DM1 immunoconjugate in 200 pl of culture media. The cells and antibody/conjugate mixtures were then incubated for 2-7 d, at which time cellviability was assessed by an MTT assay.
In Vitro Model Endocervical adenocarcinoma WISH cells CVCL_1909
Experiment 5 Reporting the Activity Date of This ADC [29]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.8 nM
Positive CA6 expression (CA6 +++/++)
Method Description
Clonogenic assays were conducted where cells (1000-2500 cells/well) were plated on6-well plates in 2 ml of conjugate diluted in culture media.The cells were continuously exposed to the conjugate at concentrations,generally between 3x10-11M toseveral 3x10-9 M,and were incubated in a 37°C,6% CO2, humidified chamber for 5-9 days.

   Click to Show/Hide
In Vitro Model Ovarian serous adenocarcinoma Caov-3 cells CVCL_0201
Experiment 6 Reporting the Activity Date of This ADC [29]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.4 nM
Positive CA6 expression (CA6 +++/++)
Method Description
Clonogenic assays were conducted where cells (1000-2500 cells/well) were plated on6-well plates in 2 ml of conjugate diluted in culture media.The cells were continuously exposed to the conjugate at concentrations,generally between 3x10-11M toseveral 3x10-9 M,and were incubated in a 37°C,6% CO2, humidified chamber for 5-9 days.

   Click to Show/Hide
In Vitro Model Human papillomavirus-related endocervical adenocarcinoma KB cells CVCL_0372
Experiment 7 Reporting the Activity Date of This ADC [29]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.61 nM
Positive CA6 expression (CA6 +++/++)
Method Description
In the MTT assay, cells were seeded in 96-well plates ata density of 1000-5000 cells/well. The cells were plated with serial dilutions of either naked muDS6 or muDS6-DM1 immunoconjugate in 200 pl of culture media. The cells and antibody/conjugate mixtures were then incubated for 2-7 d, at which time cellviability was assessed by an MTT assay.
In Vitro Model Ovarian serous adenocarcinoma Caov-3 cells CVCL_0201
Experiment 8 Reporting the Activity Date of This ADC [29]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.8 nM
Positive CA6 expression (CA6 +++/++)
Method Description
Clonogenic assays were conducted where cells (1000-2500 cells/well) were plated on6-well plates in 2 ml of conjugate diluted in culture media.The cells were continuously exposed to the conjugate at concentrations,generally between 3x10-11M toseveral 3x10-9 M,and were incubated in a 37°C,6% CO2, humidified chamber for 5-9 days.

   Click to Show/Hide
In Vitro Model Pancreatic adenocarcinoma HPAC cells CVCL_3517
Experiment 9 Reporting the Activity Date of This ADC [29]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.8 nM
Positive CA6 expression (CA6 +++/++)
Method Description
Clonogenic assays were conducted where cells (1000-2500 cells/well) were plated on6-well plates in 2 ml of conjugate diluted in culture media.The cells were continuously exposed to the conjugate at concentrations,generally between 3x10-11M toseveral 3x10-9 M,and were incubated in a 37°C,6% CO2, humidified chamber for 5-9 days.

   Click to Show/Hide
In Vitro Model Endocervical adenocarcinoma HeLa cells CVCL_0030
Experiment 10 Reporting the Activity Date of This ADC [29]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.84 nM
Positive CA6 expression (CA6 +++/++)
Method Description
In the MTT assay, cells were seeded in 96-well plates ata density of 1000-5000 cells/well. The cells were plated with serial dilutions of either naked muDS6 or muDS6-DM1 immunoconjugate in 200 pl of culture media. The cells and antibody/conjugate mixtures were then incubated for 2-7 d, at which time cellviability was assessed by an MTT assay.
In Vitro Model Pancreatic adenocarcinoma HPAC cells CVCL_3517
Experiment 11 Reporting the Activity Date of This ADC [29]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
2 nM
Positive CA6 expression (CA6 +++/++)
Method Description
Clonogenic assays were conducted where cells (1000-2500 cells/well) were plated on6-well plates in 2 ml of conjugate diluted in culture media.The cells were continuously exposed to the conjugate at concentrations,generally between 3x10-11M toseveral 3x10-9 M,and were incubated in a 37°C,6% CO2, humidified chamber for 5-9 days.

   Click to Show/Hide
In Vitro Model Ovarian clear cell adenocarcinoma TOV-21G cells CVCL_3613
Experiment 12 Reporting the Activity Date of This ADC [29]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 3 nM Positive CA6 expression (CA6 +++/++)
Method Description
Clonogenic assays were conducted where cells (1000-2500 cells/well) were plated on6-well plates in 2 ml of conjugate diluted in culture media.The cells were continuously exposed to the conjugate at concentrations,generally between 3x10-11M toseveral 3x10-9 M,and were incubated in a 37°C,6% CO2, humidified chamber for 5-9 days.

   Click to Show/Hide
In Vitro Model Invasive breast carcinoma ZR-75-1 cells CVCL_0588
Experiment 13 Reporting the Activity Date of This ADC [29]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 3 nM Positive CA6 expression (CA6 +++/++)
Method Description
Clonogenic assays were conducted where cells (1000-2500 cells/well) were plated on6-well plates in 2 ml of conjugate diluted in culture media.The cells were continuously exposed to the conjugate at concentrations,generally between 3x10-11M toseveral 3x10-9 M,and were incubated in a 37°C,6% CO2, humidified chamber for 5-9 days.

   Click to Show/Hide
In Vitro Model Invasive breast carcinoma T-47D cells CVCL_0553
Experiment 14 Reporting the Activity Date of This ADC [29]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 3 nM Positive CA6 expression (CA6 +++/++)
Method Description
Clonogenic assays were conducted where cells (1000-2500 cells/well) were plated on6-well plates in 2 ml of conjugate diluted in culture media.The cells were continuously exposed to the conjugate at concentrations,generally between 3x10-11M toseveral 3x10-9 M,and were incubated in a 37°C,6% CO2, humidified chamber for 5-9 days.

   Click to Show/Hide
In Vitro Model Ovarian serous adenocarcinoma OVCAR-5 cells CVCL_1628
Experiment 15 Reporting the Activity Date of This ADC [29]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 3 nM Positive CA6 expression (CA6 +++/++)
Method Description
Clonogenic assays were conducted where cells (1000-2500 cells/well) were plated on6-well plates in 2 ml of conjugate diluted in culture media.The cells were continuously exposed to the conjugate at concentrations,generally between 3x10-11M toseveral 3x10-9 M,and were incubated in a 37°C,6% CO2, humidified chamber for 5-9 days.

   Click to Show/Hide
In Vitro Model Pancreatic adenocarcinoma Hs 766T cells CVCL_0334
Experiment 16 Reporting the Activity Date of This ADC [29]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 3 nM Positive CA6 expression (CA6 +++/++)
Method Description
Clonogenic assays were conducted where cells (1000-2500 cells/well) were plated on6-well plates in 2 ml of conjugate diluted in culture media.The cells were continuously exposed to the conjugate at concentrations,generally between 3x10-11M toseveral 3x10-9 M,and were incubated in a 37°C,6% CO2, humidified chamber for 5-9 days.

   Click to Show/Hide
In Vitro Model Pancreatic ductal adenocarcinoma HPAF-II cells CVCL_0313
Experiment 17 Reporting the Activity Date of This ADC [29]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 3 nM Positive CA6 expression (CA6 +++/++)
Method Description
Clonogenic assays were conducted where cells (1000-2500 cells/well) were plated on6-well plates in 2 ml of conjugate diluted in culture media.The cells were continuously exposed to the conjugate at concentrations,generally between 3x10-11M toseveral 3x10-9 M,and were incubated in a 37°C,6% CO2, humidified chamber for 5-9 days.

   Click to Show/Hide
In Vitro Model High grade ovarian serous adenocarcinoma Caov-4 cells CVCL_0202
Experiment 18 Reporting the Activity Date of This ADC [29]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 3 nM Positive CA6 expression (CA6 +++/++)
Method Description
Clonogenic assays were conducted where cells (1000-2500 cells/well) were plated on6-well plates in 2 ml of conjugate diluted in culture media.The cells were continuously exposed to the conjugate at concentrations,generally between 3x10-11M toseveral 3x10-9 M,and were incubated in a 37°C,6% CO2, humidified chamber for 5-9 days.

   Click to Show/Hide
In Vitro Model Invasive breast carcinoma of no special type BT-20 cells CVCL_0178
Experiment 19 Reporting the Activity Date of This ADC [29]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
3.01 nM
Positive CA6 expression (CA6 +++/++)
Method Description
In the MTT assay, cells were seeded in 96-well plates ata density of 1000-5000 cells/well. The cells were plated with serial dilutions of either naked muDS6 or muDS6-DM1 immunoconjugate in 200 pl of culture media. The cells and antibody/conjugate mixtures were then incubated for 2-7 d, at which time cellviability was assessed by an MTT assay.
In Vitro Model Human papillomavirus-related endocervical adenocarcinoma KB cells CVCL_0372
Experiment 20 Reporting the Activity Date of This ADC [29]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
6.88 nM
Positive CA6 expression (CA6 +++/++)
Method Description
In the MTT assay, cells were seeded in 96-well plates ata density of 1000-5000 cells/well. The cells were plated with serial dilutions of either naked muDS6 or muDS6-DM1 immunoconjugate in 200 pl of culture media. The cells and antibody/conjugate mixtures were then incubated for 2-7 d, at which time cellviability was assessed by an MTT assay.
In Vitro Model Ovarian clear cell adenocarcinoma TOV-21G cells CVCL_3613
Experiment 21 Reporting the Activity Date of This ADC [29]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
10 nM
Positive CA6 expression (CA6 +++/++)
Method Description
In the MTT assay, cells were seeded in 96-well plates ata density of 1000-5000 cells/well. The cells were plated with serial dilutions of either naked muDS6 or muDS6-DM1 immunoconjugate in 200 pl of culture media. The cells and antibody/conjugate mixtures were then incubated for 2-7 d, at which time cellviability was assessed by an MTT assay.
In Vitro Model Pancreatic ductal adenocarcinoma HPAF-II cells CVCL_0313
Experiment 22 Reporting the Activity Date of This ADC [29]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
14.4 nM
Positive CA6 expression (CA6 +++/++)
Method Description
In the MTT assay, cells were seeded in 96-well plates ata density of 1000-5000 cells/well. The cells were plated with serial dilutions of either naked muDS6 or muDS6-DM1 immunoconjugate in 200 pl of culture media. The cells and antibody/conjugate mixtures were then incubated for 2-7 d, at which time cellviability was assessed by an MTT assay.
In Vitro Model Invasive breast carcinoma of no special type BT-20 cells CVCL_0178
Experiment 23 Reporting the Activity Date of This ADC [29]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 30 nM Positive CA6 expression (CA6 +++/++)
Method Description
In the MTT assay, cells were seeded in 96-well plates ata density of 1000-5000 cells/well. The cells were plated with serial dilutions of either naked muDS6 or muDS6-DM1 immunoconjugate in 200 pl of culture media. The cells and antibody/conjugate mixtures were then incubated for 2-7 d, at which time cellviability was assessed by an MTT assay.
In Vitro Model Invasive breast carcinoma T-47D cells CVCL_0553
Experiment 24 Reporting the Activity Date of This ADC [29]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 30 nM Positive CA6 expression (CA6 +++/++)
Method Description
In the MTT assay, cells were seeded in 96-well plates ata density of 1000-5000 cells/well. The cells were plated with serial dilutions of either naked muDS6 or muDS6-DM1 immunoconjugate in 200 pl of culture media. The cells and antibody/conjugate mixtures were then incubated for 2-7 d, at which time cellviability was assessed by an MTT assay.
In Vitro Model Endocervical adenocarcinoma HeLa cells CVCL_0030
Experiment 25 Reporting the Activity Date of This ADC [29]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 30 nM Positive CA6 expression (CA6 +++/++)
Method Description
In the MTT assay, cells were seeded in 96-well plates ata density of 1000-5000 cells/well. The cells were plated with serial dilutions of either naked muDS6 or muDS6-DM1 immunoconjugate in 200 pl of culture media. The cells and antibody/conjugate mixtures were then incubated for 2-7 d, at which time cellviability was assessed by an MTT assay.
In Vitro Model High grade ovarian serous adenocarcinoma Caov-4 cells CVCL_0202
Experiment 26 Reporting the Activity Date of This ADC [29]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 30 nM Positive CA6 expression (CA6 +++/++)
Method Description
In the MTT assay, cells were seeded in 96-well plates ata density of 1000-5000 cells/well. The cells were plated with serial dilutions of either naked muDS6 or muDS6-DM1 immunoconjugate in 200 pl of culture media. The cells and antibody/conjugate mixtures were then incubated for 2-7 d, at which time cellviability was assessed by an MTT assay.
In Vitro Model Ductal carcinoma BT-483 cells CVCL_2319
Experiment 27 Reporting the Activity Date of This ADC [29]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
32 nM
Positive CA6 expression (CA6 +++/++)
Method Description
In the MTT assay, cells were seeded in 96-well plates ata density of 1000-5000 cells/well. The cells were plated with serial dilutions of either naked muDS6 or muDS6-DM1 immunoconjugate in 200 pl of culture media. The cells and antibody/conjugate mixtures were then incubated for 2-7 d, at which time cellviability was assessed by an MTT assay.
In Vitro Model Pancreatic adenocarcinoma Hs 766T cells CVCL_0334
Experiment 28 Reporting the Activity Date of This ADC [29]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
846 nM
Positive CA6 expression (CA6 +++/++)
Method Description
In the MTT assay, cells were seeded in 96-well plates ata density of 1000-5000 cells/well. The cells were plated with serial dilutions of either naked muDS6 or muDS6-DM1 immunoconjugate in 200 pl of culture media. The cells and antibody/conjugate mixtures were then incubated for 2-7 d, at which time cellviability was assessed by an MTT assay.
In Vitro Model Ovarian serous adenocarcinoma OVCAR-5 cells CVCL_1628
B4-SPP-DC1 [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [25]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.4 pM
Positive CD19 expression (CD19+++/++)
Method Description
Cytotoxicity of B4-SPP-DCx Conjugates (without acid phosphatase treatment) against Ramos (Ag+) and HL60/s (Ag-) Cells.
In Vitro Model Burkitt lymphoma Ramos cells CVCL_0597
Experiment 2 Reporting the Activity Date of This ADC [25]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.3 nM
Negative CD19 expression(CD19-)
Method Description
Cytotoxicity of B4-SPP-DCx Conjugates (without acid phosphatase treatment) against Ramos (Ag+) and HL60/s (Ag-) Cells.
In Vitro Model Adult acute myeloid leukemia HL-60 cells CVCL_0002
CNTO95-SPP-DM4 [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 [22]
Efficacy Data Half Maximal Effective Concentration (EC50)
1 ug/mL
Positive ITGAV expression (ITGAV +++/++)
Method Description
Cells were seeded into white 96-well tissue culture plates (5000 cells/well)in culture medium and incubated for 16 hrs. Serial dilutions of immunoconjugates were added toeach appropraite wells (0-20 ug/ml). Tissue culture plates were incubated at 37°C for 96 hrs.
In Vitro Model Colon cancer HT29 cells CVCL_A8EZ
Experiment 2 Reporting the Activity Date of This ADC [22]
Efficacy Data Half Maximal Effective Concentration (EC50)
1.5 ug/mL
Positive ITGAV expression (ITGAV +++/++)
Method Description
Cells were seeded into white 96-well tissue culture plates (5000 cells/well)in culture medium and incubated for 16 hrs. Serial dilutions of immunoconjugates were added toeach appropraite wells (0-20 ug/ml). Tissue culture plates were incubated at 37°C for 96 hrs.
In Vitro Model Lung adenocarcinoma A-549 cells CVCL_0023
Experiment 3 Reporting the Activity Date of This ADC [22]
Efficacy Data Half Maximal Effective Concentration (EC50)
0.29 mg/mL
Positive ITGAV expression (ITGAV +++/++)
Method Description
Cells were harvested, rinsedsuspended in serum free DMEM, and sequentially incubated for 60 minutes on ice with serialdiluted CNTO 95,CNTO 364, CNTO 365 and CNTO 366 and FITC-labeled anti-humanantibody (10 mg/ml).
In Vitro Model Colon cancer HT29 cells CVCL_A8EZ
Experiment 4 Reporting the Activity Date of This ADC [22]
Efficacy Data Half Maximal Effective Concentration (EC50)
0.3 mg/mL
Positive ITGAV expression (ITGAV +++/++)
Method Description
Cells were harvested, rinsedsuspended in serum free DMEM, and sequentially incubated for 60 minutes on ice with serialdiluted CNTO 95,CNTO 364, CNTO 365 and CNTO 366 and FITC-labeled anti-humanantibody (10 mg/ml).
In Vitro Model Ovarian endometrioid adenocarcinoma A2780 cells CVCL_0134
Experiment 5 Reporting the Activity Date of This ADC [22]
Efficacy Data Half Maximal Effective Concentration (EC50)
0.42 mg/mL
Positive ITGAV expression (ITGAV +++/++)
Method Description
Cells were harvested, rinsedsuspended in serum free DMEM, and sequentially incubated for 60 minutes on ice with serialdiluted CNTO 95,CNTO 364, CNTO 365 and CNTO 366 and FITC-labeled anti-humanantibody (10 mg/ml).
In Vitro Model Lung adenocarcinoma A-549 cells CVCL_0023
References
Ref 1 An Open-label Phase II Study of Lorvotuzumab Mertansine
Ref 2 BB-10901 in Treating Patients With Relapsed and/or Refractory Multiple Myeloma
Ref 3 IMGN901 in Combination With Lenalidomide and Dexamethasone
Ref 4 Lorvotuzumab Mertansine in Treating Younger Patients With Relapsed or Refractory Wilms Tumor, Rhabdomyosarcoma, Neuroblastoma, Pleuropulmonary Blastoma, Malignant Peripheral Nerve Sheath Tumor, or Synovial Sarcoma
Ref 5 Phase 1/2 Study of the CD56-Targeting Antibody-Drug Conjugate Lorvotuzumab Mertansine (IMGN901) in Combination With Carboplatin/Etoposide in Small-Cell Lung Cancer Patients With Extensive-Stage Disease
Ref 6 BB-10901 in Treating Patients With Relapsed or Refractory Solid Tumors
Ref 7 A Phase I Study to Assess the Safety and Pharmacokinetics of Single-agent Lorvotuzumab Mertansine (IMGN901) in Patients with Relapsed and/or Refractory CD-56-positive Multiple Myeloma. Clin Lymphoma Myeloma Leuk. 2019 Jan;19(1):29-34. doi: 10.1016/j.clml.2018.08.018. Epub 2018 Sep 5.
Ref 8 A Trial of MLN2704 in Subjects With Metastatic Androgen Independent Prostate Cancer
Ref 9 Phase 1/2 multiple ascending dose trial of the prostate-specific membrane antigen-targeted antibody drug conjugate MLN2704 in metastatic castration-resistant prostate cancer
Ref 10 Dose Escalation of Bivatuzumab Mertansine in Patients With Advanced Squamous Cell Carcinoma of the Head and Neck or Esophagus
Ref 11 Single Dose Escalation Study of Bivatuzumab Mertansine in Female Patients With CD44v6 Positive Metastatic Breast Cancer
Ref 12 Dose Escalation of Bivatuzumab Mertansine in Female Patients With CD44v6 Positive Recurrent or Metastatic Breast Cancer
Ref 13 Single Dose Escalation Study of Bivatuzumab Mertansine in Patients With Advanced Squamous Cell Carcinoma of the Head and Neck
Ref 14 Safety and pharmacokinetics of bivatuzumab mertansine in patients with CD44v6-positive metastatic breast cancer: final results of a phase I study. Anticancer Drugs. 2007 Apr;18(4):477-85.
Ref 15 Cantuzumab mertansine in a three-times a week schedule: a phase I and pharmacokinetic study. Cancer Chemother Pharmacol. 2008 Oct;62(5):911-9.
Ref 16 Phase I trial with the CD44v6-targeting immunoconjugate bivatuzumab mertansine in head and neck squamous cell carcinoma. Oral Oncol. 2008 Sep;44(9):823-9.
Ref 17 An Open Phase I Dose Escalation Study of Bivatuzumab Mertansine Administered Intravenously Once Per Week for Three Weeks in Patients With Advanced Squamous Cell Carcinoma of the Head and Neck or Esophagus With Repeated Administration Courses in Patients With Clinical Benefit
Ref 18 An Open Phase I Dose Escalation Study of Bivatuzumab Mertansine Administered Intravenously Once Per Week for Three Weeks in Female Patients With CD44v6 Positive Recurrent or Metastatic Breast Cancer With Repeated Administration Courses in Patients With Clinical Benefit
Ref 19 An Open Phase I Single Dose Escalation Study of Bivatuzumab Mertansine Administered Intravenously in Female Patients With CD44v6 Positive Metastatic Breast Cancer With Repeated Administration in Patients With Clinical Benefit
Ref 20 An Open Phase I Single Dose Escalation Study of Bivatuzumab Mertansine Administered Intravenously in Patients With Advanced Squamous Cell Carcinoma of the Head and Neck With Repeated Administration in Patients With Clinical Benefit
Ref 21 Cantuzumab mertansine, a maytansinoid immunoconjugate directed to the CanAg antigen: a phase I, pharmacokinetic, and biologic correlative study. J Clin Oncol. 2003 Jan 15;21(2):211-22.
Ref 22 Anti-integrin immunoconjugates, methods and uses; 2008-01-17.
Ref 23 IMGN853, a Folate Receptor- (FR)-Targeting Antibody-Drug Conjugate, Exhibits Potent Targeted Antitumor Activity against FR-Expressing Tumors. Mol Cancer Ther. 2015 Jul;14(7):1605-13.
Ref 24 Antibody drug conjugates.
Ref 25 Synthesis and biological evaluation of antibody conjugates of phosphate prodrugs of cytotoxic DNA alkylators for the targeted treatment of cancer. J Med Chem. 2012 Jan 26;55(2):766-82. doi: 10.1021/jm201284m.
Ref 26 Immunoconjugates targeting cd138 and uses thereof; 2009-07-02.
Ref 27 Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate. Cancer Res. 2008 Nov 15;68(22):9280-90.
Ref 28 Folate receptor 1 antibodies and immunoconjugates and uses thereof; 2011-09-01.
Ref 29 CA6 antigen-specific cytotoxic conjugate and methods of using the same; 2017-11-21.