Linker Information
General Information of This Linker
Linker ID |
LIN0ZGCUP
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Linker Name |
CL2A
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Linker Type |
pH-sensitive linker
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Antibody-Linker Relation |
Cleavable
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Structure | ||||||
Formula |
C50H79N9O16
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Isosmiles |
C1CC(CCC1CN2C(=O)C=CC2=O)C(=O)NCC3=CN(N=N3)CCOCCOCCOCCOCCOCCOCCOCCOCCNC(=O)COCC(=O)N[C@@H](CCCCN)C(=O)NC4=CC=C(C=C4)CO
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PubChem CID | ||||||
InChI |
InChI=1S/C50H79N9O16/c51-14-2-1-3-44(50(66)54-42-10-6-40(36-60)7-11-42)55-46(62)38-75-37-45(61)52-15-17-67-19-21-69-23-25-71-27-29-73-31-32-74-30-28-72-26-24-70-22-20-68-18-16-58-35-43(56-57-58)33-53-49(65)41-8-4-39(5-9-41)34-59-47(63)12-13-48(59)64/h6-7,10-13,35,39,41,44,60H,1-5,8-9,14-34,36-38,51H2,(H,52,61)(H,53,65)(H,54,66)(H,55,62)/t39?,41?,44-/m0/s1
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InChIKey |
CJDCJOXHKQMGGB-DBSIFAAZSA-N
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IUPAC Name |
N-[[1-[2-[2-[2-[2-[2-[2-[2-[2-[2-[[2-[2-[[(2S)-6-amino-1-[4-(hydroxymethyl)anilino]-1-oxohexan-2-yl]amino]-2-oxoethoxy]acetyl]amino]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl]triazol-4-yl]methyl]-4-[(2,5-dioxopyrrol-1-yl)methyl]cyclohexane-1-carboxamide
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Pharmaceutical Properties |
Molecule Weight
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1062.2
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Polar area
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314
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Complexity
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1620
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xlogp Value
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-3
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Heavy Count
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75
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Rot Bonds
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44
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Hbond acc
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19
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Hbond Donor
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6
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Each Antibody-drug Conjugate Related to This Linker
Full Information of The Activity Data of The ADC(s) Related to This Linker
Sacituzumab govitecan [Approved]
Identified from the Human Clinical Data
Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
Efficacy Data | Objective Response Rate (ORR) |
21.00%
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Patients Enrolled |
Patients had histologically locally confirmed measurable HR+/HER2 MBC and 2-4 prior systemic chemotherapy regimens for metastatic disease. (Neo)adjuvant therapy for early-stage disease qualified as one of the required prior chemotherapy regimens if the development of unresectable, locally advanced, or metastatic disease occurred within 12 months of therapy (early relapse). Patients must have previously received at least one taxane, at least one anticancer hormonal treatment, and at least one CDK4/6i.
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Administration Dosage |
10 mg/kg intravenously once weekly on day 1 and day 8 every 21 days.
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Related Clinical Trial | |||||
NCT Number | NCT03901339 | Clinical Status | Phase 3 | ||
Clinical Description |
Phase 3 study of sacituzumab govitecan (IMMU-132) versus treatment of physician's choice (tpc) in subjects with hormonal receptor-positive (hr+) human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer (MBC) who have failed at least two prior chemotherapy regimens.
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Primary Endpoint |
medium PFS=5.50 months.
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Other Endpoint |
medium OS=13.90 months.
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Experiment 2 Reporting the Activity Date of This ADC | [2] | ||||
Efficacy Data | Objective Response Rate (ORR) |
31.43%
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Patients Enrolled |
Patients had metastatic triple-negative breast cancer (mTNBC) that had progressed following 2 prior standard chemotherapy regimens (no upper limit) for unresectable, locally advanced, or metastatic disease, and included a taxane (any setting). Per protocol, patients were also eligible after only one prior regimen in the metastatic setting if their disease recurred within 12 months of completing (neo)adjuvant therapy.
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Administration Dosage |
10 mg/kg on days 1 and 8 of 21-day cycles; until progression, unacceptable toxicity, study withdrawal, or death.
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Related Clinical Trial | |||||
NCT Number | NCT02574455 | Clinical Status | Phase 3 | ||
Clinical Description |
Analysis of patients without and with an initial triple-negative breast cancer diagnosis in the phase 3 randomized ASCENT study of sacituzumab govitecan in metastatic triple-negative breast cancer.
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Primary Endpoint |
PFS=4.60 months for patients without TNBC at initial diagnosis PFS=5.70 months for patients with TNBC at initial diagnosis.
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Other Endpoint |
ORR=31.43%.
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Experiment 3 Reporting the Activity Date of This ADC | [3] | ||||
Efficacy Data | Objective Response Rate (ORR) |
35.00%
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Patients Enrolled |
Patients with metastatic triple-negative breast cancer that was relapsed or refractory to two or more previous standard chemotherapy regimens (no upper limit) for unresectable, locally advanced or metastatic disease; previous therapy had to include a taxane (for any indication). Patients had to have triple-negative breast cancer according to standard American Society of Clinical OncologyCollege of American Pathologists criteria.
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Administration Dosage |
Sacituzumab govitecan at a dose of 10 mg per kilogram of body weight intravenously on days 1 and 8 of each 21-day cycle.
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Related Clinical Trial | |||||
NCT Number | NCT02574455 | Clinical Status | Phase 3 | ||
Clinical Description |
An international, multi-center, open-label, randomized, phase 3 trial of sacituzumab govitecan versus treatment of physician choice in patients with metastatic triple-negative breast cancer who received at least two prior treatments.
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Primary Endpoint |
Progression-free survival=5.60 months,(95% CI, 4.30-6.30) with sacituzumab govitecan and 1.70 months (95% CI,1.50 to 2.60) with chemotherapy (hazard ratio for disease progression or death, 0.41; 95% CI, 0.32-0.52).
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Other Endpoint |
The percentage of patients with an objective response was 35.00% with sacituzumab govitecan and 5.00% with chemotherapy.
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Experiment 4 Reporting the Activity Date of This ADC | [4] | ||||
Efficacy Data | Objective Response Rate (ORR) |
38.80%
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High TROP2 expression (TROP2+++) | ||
Patients Enrolled |
Histologically or cytologically confirmed metastatic triple negative breast cancer (mTNBC); refractory or relapsing after 2 prior standard chemotherapy for unresectable, locally advanced, or metastatic disease, including a taxane (any setting).
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Administration Dosage |
10 mg/kg intravenously on Days 1 and 8 of each 21-day treatment cycle.
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Related Clinical Trial | |||||
NCT Number | NCT04454437 | Clinical Status | Phase 2 | ||
Clinical Description |
A phase IIb, single arm, multicenter trial of sacituzumab govitecan in chinese patients with metastatic triple-negative breast cancer who received at least two prior treatments.
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Primary Endpoint |
Objective response rate=38.80% (95% CI 28.06-50.30), clinical benefit rate=43.80% (95% CI 32.68-55.30).
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Other Endpoint |
Median PFS=5.55 months (95% CI 4.14-N/A).
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Experiment 5 Reporting the Activity Date of This ADC | [5] | ||||
Efficacy Data | Objective Response Rate (ORR) |
14.00%
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Patients Enrolled |
Patients 18 years of age with mSCLC who had relapsed or were refractory to at least one prior standard line of therapy for metastatic disease, and with measurable tumors by CT, were enrolled. They were required to have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, adequate bone marrow, hepatic and renal function, and other eligibility as described in the phase I trial (25). Previous therapy had to be completed at least 2 weeks before enrollment.
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Administration Dosage |
Either 8 or 10 mg/kg i.v. on days 1 and 8 of 21-day cycles.
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Related Clinical Trial | |||||
NCT Number | NCT01631552 | Clinical Status | Phase 1 | ||
Clinical Description |
A phase 1/2 study of IMMU-132 (hRS7-SN38 antibody drug conjugate) in patients with epithelial cancer.
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Primary Endpoint |
OrR=14.00% (17.00% for 10 mg/kg group).
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Other Endpoint |
The median response duration=5.70 months; the clinical benefit rate (CBR>4 months), 34.00%; median PFS=3.70 months; median OS=7.50 months.
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Experiment 6 Reporting the Activity Date of This ADC | [6] | ||||
Efficacy Data | Objective Response Rate (ORR) |
17.70% (small-cell lung cancer)
22.20% (endometrial cancer) 9.10% (castrate-resistant prostate cancer) |
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Patients Enrolled |
Patients were >18 years of age with metastatic cancer [cervical, clear-cell renal, CRC, epithelial ovarian, endometrial, esophageal, gastric, hepatocellular, CRPC, pancreatic ductal adenocarcinoma, squamous cell head and neck, thyroid, urothelial (UC) cancer; glioblastoma multiforme; mTNBC or non-mTNBC; and SCLC or NSCLC] who had relapsed after or were refractory to at least one prior standard therapeutic regimen.
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Administration Dosage |
Intravenous 8, 10, 12, or 18 mg/kg on days 1 and 8 of 21-day cycles until disease progression or unacceptable toxicity.
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Related Clinical Trial | |||||
NCT Number | NCT01631552 | Clinical Status | Phase 1 | ||
Clinical Description |
A phase 1/2 study of IMMU-132 (hRS7-SN38 antibody drug conjugate) in patients with epithelial cancer.
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Primary Endpoint |
Safety and pharmacokinetic parameters with investigator-evaluated objective response rate.
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Other Endpoint |
Efficacy endpoints included: ORR, which included both confirmed partial response (PR) and complete response (CR).
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Experiment 7 Reporting the Activity Date of This ADC | [7] | ||||
Efficacy Data | Objective Response Rate (ORR) |
19.00%
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Patients Enrolled |
Patients 18 years with mNSCLC who had measurable disease and progressed after at least one line of therapy for stage IV disease were enrolled. Requirements included Eastern Cooperative Oncology Group performance status 0 or 1, adequate bone marrow and hepatic and renal function, and other eligibility criteria as described in the phase I trial. Prior systemic therapy had to be completed at least 4 weeks before enrollment.
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Administration Dosage |
Doses of 8 or 10 mg/kg were given on days 1 and 8 of 21-day cycles; intravenously.
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Related Clinical Trial | |||||
NCT Number | NCT01631552 | Clinical Status | Phase 1 | ||
Clinical Description |
A phase 1/2 study of IMMU-132 (hRS7-SN38 antibody drug conjugate) in patients with epithelial cancer.
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Primary Endpoint |
Safety and objective response rate (ORR).
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Other Endpoint |
Progression-free survival and overall survival.
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Experiment 8 Reporting the Activity Date of This ADC | [8] | ||||
Efficacy Data | Objective Response Rate (ORR) |
30.00%
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Patients Enrolled |
Patients 18 years of age who had mTNBC refractory to or relapsed after at least one standard line of therapy since diagnosis and measurable disease by computed tomography scan (or magnetic resonance imaging). patients had an Eastern Cooperative Oncology Group performance status of 0 or 1, adequate bone marrow, hepatic and renal function, and prior toxicities at study entry of grade 1 by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. Patients with brain metastasis were excluded, unless treated and without progression, and were not receiving high-dose corticosteroids for at least 4 weeks.
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Administration Dosage |
10 mg/kg starting dose on days 1 and 8 of 21-day repeated cycles; intravenously; eight cycles.
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Related Clinical Trial | |||||
NCT Number | NCT01631552 | Clinical Status | Phase 1 | ||
Clinical Description |
A phase 1/2 study of IMMU-132 (hRS7-SN38 antibody drug conjugate) in patients with epithelial cancer.
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Primary Endpoint |
Safety and objective response rate.
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Other Endpoint |
Progression-free survival and overall survival.
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Experiment 9 Reporting the Activity Date of This ADC | [9] | ||||
Efficacy Data | Objective Response Rate (ORR) |
33.30%
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Patients Enrolled |
Metastatic triple-negative breast cancer.
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Administration Dosage |
10 mg per kilogram intravenously on days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxic effects.
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Related Clinical Trial | |||||
NCT Number | NCT01631552 | Clinical Status | Phase 1 | ||
Clinical Description |
A phase 1/2 study of IMMU-132 (hRS7-SN38 antibody drug conjugate) in patients with epithelial cancer.
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Primary Endpoint |
Objective response rate=33.3% (95% confidence interval [CI].
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Other Endpoint |
The median duration of response=7.70 months (95% CI, 4.90 to 10.08),clinical benefit rate = 45.40%.
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Experiment 10 Reporting the Activity Date of This ADC | [10] | ||||
Related Clinical Trial | |||||
NCT Number | NCT01631552 | Clinical Status | Phase 1 | ||
Clinical Description |
A phase 1/2 study of IMMU-132 (hRS7-SN38 antibody drug conjugate) in patients with epithelial cancer.
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Discovered Using Patient-derived Xenograft Model
Experiment 1 Reporting the Activity Date of This ADC | [11] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
2.14 nM
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Method Description |
Antibody-dependent cell cytotoxicity (ADCC) against Trop-2-positive and Trop-2-negative EC cell lines was measured in vitro,compared to control ADC (P = 0.014 and P = 0.005).
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In Vivo Model | Endometrioma PDX model (PDX: END(K)265) |
Revealed Based on the Cell Line Data
Experiment 1 Reporting the Activity Date of This ADC | [12] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
0.18-0.26 nM
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Method Description |
Two Trop-2 positive (CVX-8, ADX-3), and one Trop-2 negative (ADX-2) cell lines were used. A cell line with a strong Trop-2 expression (CVX-8) was used to test in vivo antitumor activity in xenografts models,in vitro experiments.
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In Vitro Model | Primary cervical cancer | Primary cervical cancer cells | Homo sapiens | ||
Experiment 2 Reporting the Activity Date of This ADC | [13] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
0.60 nM
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Method Description |
The inhibitory activity of sacituzumab govitecan govitecan against USC with heterogeneous Trop-2 expression was tested by admixing ARK2 USC cells (i.e., high Trop-2 expression) compared to control ADC (p< 0.05),in vitro.
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In Vitro Model | Endometrial serous adenocarcinoma | USPC-ARK-2 cells | CVCL_IV73 | ||
Experiment 3 Reporting the Activity Date of This ADC | [14] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
1.02 nM
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Method Description |
Briefly, cells were plated into 96-well clear, flat-bottomed plates. The immunoconjugate reconstituted in media was diluted with media to a final concentration of range of 0.004 to 250 nM in the wells. Plates were incubated in humidified chamber for 96 h 37°C/5% CO2. Growth inhibition was measured as a percent of growth relative to untreated cells.
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In Vitro Model | Colon adenocarcinoma | COLO 205 cells | CVCL_0218 | ||
Experiment 4 Reporting the Activity Date of This ADC | [14] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
1.44 nM
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Method Description |
Briefly, cells were plated into 96-well clear, flat-bottomed plates. The immunoconjugate reconstituted in media was diluted with media to a final concentration of range of 0.004 to 250 nM in the wells. Plates were incubated in humidified chamber for 96 h 37°C/5% CO2. Growth inhibition was measured as a percent of growth relative to untreated cells.
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In Vitro Model | Pancreatic ductal adenocarcinoma | BxPC-3 cells | CVCL_0186 | ||
Experiment 5 Reporting the Activity Date of This ADC | [14] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
1.86 nM
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Method Description |
Briefly, cells were plated into 96-well clear, flat-bottomed plates. The immunoconjugate reconstituted in media was diluted with media to a final concentration of range of 0.004 to 250 nM in the wells. Plates were incubated in humidified chamber for 96 h 37°C/5% CO2. Growth inhibition was measured as a percent of growth relative to untreated cells.
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In Vitro Model | Prostate carcinoma | PC-3 cells | CVCL_0035 | ||
Experiment 6 Reporting the Activity Date of This ADC | [14] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
3.50 nM
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Method Description |
Briefly, cells were plated into 96-well clear, flat-bottomed plates. The immunoconjugate reconstituted in media was diluted with media to a final concentration of range of 0.004 to 250 nM in the wells. Plates were incubated in humidified chamber for 96 h 37°C/5% CO2. Growth inhibition was measured as a percent of growth relative to untreated cells.
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In Vitro Model | Pancreatic ductal adenocarcinoma | Capan-1 cells | CVCL_0237 | ||
Experiment 7 Reporting the Activity Date of This ADC | [15] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
3.90 nM
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Method Description |
The inhibitory activity of sacituzumab govitecan govitecan against USC with heterogeneous Trop-2 expression was tested by admixing ARK2 USC cells (i.e., high Trop-2 expression) compared to control ADC (p< 0.05),in vitro.
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In Vitro Model | Endometrial serous adenocarcinoma | USPC-ARK-2 cells | CVCL_IV73 | ||
Experiment 8 Reporting the Activity Date of This ADC | [14] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
7.19 nM
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Method Description |
Briefly, cells were plated into 96-well clear, flat-bottomed plates. The immunoconjugate reconstituted in media was diluted with media to a final concentration of range of 0.004 to 250 nM in the wells. Plates were incubated in humidified chamber for 96 h 37°C/5% CO2. Growth inhibition was measured as a percent of growth relative to untreated cells.
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In Vitro Model | Lung adenocarcinoma | Calu-3 cells | CVCL_0609 | ||
Experiment 9 Reporting the Activity Date of This ADC | [14] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
8.61 nM
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Method Description |
Briefly, cells were plated into 96-well clear, flat-bottomed plates. The immunoconjugate reconstituted in media was diluted with media to a final concentration of range of 0.004 to 250 nM in the wells. Plates were incubated in humidified chamber for 96 h 37°C/5% CO2. Growth inhibition was measured as a percent of growth relative to untreated cells.
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In Vitro Model | Lung squamous cell carcinoma | SK-MES-1 cells | CVCL_0630 |
Labetuzumab govitecan [Phase 2]
Identified from the Human Clinical Data
Experiment 1 Reporting the Activity Date of This ADC | [16] | ||||
Patients Enrolled |
Relapsed or refractory metastatic colorectal cancer (mCRC) who had received at least one prior irinotecan-containing regimen.
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Administration Dosage |
Once weekly at 8 and 10 mg/kg, or two times per week at 4 and 6 mg/km on weeks 1 and 2 of 3-week repeated cycles, intravenous.
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Related Clinical Trial | |||||
NCT Number | NCT01605318 | Clinical Status | Phase 1 | ||
Clinical Description |
A phase 1/2 study of once or twice weekly IMMU-130 (hMN-14-SN38, antibody-drug conjugate) in patients with colorectal cancer.
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Primary Endpoint |
The median PFS for all 86 patients was 3.60 months (95% CI,2.00 months to 4.00 months), with 16.8% (14 of 86) remaining progression free for at least 6 months, including three patients who maintained this status for at least 1 year. The median OS was 6.90 months (95% CI, 5.70 months to 7.80 months), with 24.41% (21 of 86) surviving for at least 1 year, including three patients who survived at least 2 years (one for 3 years).
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Other Endpoint |
In the regorafenib subset (n = 23), the median PFS and OS were 3.90 and 6.70 months, respectively.
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Revealed Based on the Cell Line Data
Experiment 1 Reporting the Activity Date of This ADC | [17] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
1.23 nM
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Method Description |
The inhibitory activity of IMMU-130 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated 4 days.
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In Vitro Model | Prostate carcinoma | 22RV1 cells | CVCL_1045 | ||
Experiment 2 Reporting the Activity Date of This ADC | [17] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
4.04 nM
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Method Description |
The inhibitory activity of IMMU-130 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated 4 days.
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In Vitro Model | Prostate carcinoma | DU145 cells | CVCL_0105 | ||
Experiment 3 Reporting the Activity Date of This ADC | [17] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
140.00 nM
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Method Description |
The inhibitory activity of IMMU-130 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated 4 days.
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In Vitro Model | Prostate cancer | MSKCC EF1 cells | Homo sapiens | ||
Experiment 4 Reporting the Activity Date of This ADC | [17] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
3.32 uM
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Method Description |
The inhibitory activity of IMMU-130 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated 4 days.
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In Vitro Model | Prostate small cell carcinoma | NCI-H660 cells | CVCL_1576 |
Epratuzumab-SN38 [Phase 1]
Revealed Based on the Cell Line Data
Experiment 1 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
0.06 nM
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High CD22 expression (CD22+++; Median fluorescence=145.0) | ||
Method Description |
To assess the prospect for enhanced cytotoxicity when EmabSN-38 is combined with unconjugated anti-CD20 antibody,cells were co-incubated with veltuzumab (anti-CD20 IgG) and increasing concentrations of EmabSN-38. Humanized RS7 (hRS7) anti-Trop-2 is a nonbinding human IgG1. The test drug was Emab-SN-38 + Vmab (133 nmol/L).
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In Vitro Model | Burkitt lymphoma | Daudi cells | CVCL_0008 | ||
Experiment 2 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
0.19 nM
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Moderate CD22 expression (CD22++; Median fluorescence=45.9) | ||
Method Description |
To assess the prospect for enhanced cytotoxicity when EmabSN-38 is combined with unconjugated anti-CD20 antibody,cells were co-incubated with veltuzumab (anti-CD20 IgG) and increasing concentrations of EmabSN-38. Humanized RS7 (hRS7) anti-Trop-2 is a nonbinding human IgG1. The test drug was Emab-SN-38 + Vmab (1330 nmol/L).
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In Vitro Model | EBV-related Burkitt lymphoma | Raji cells | CVCL_0511 | ||
Experiment 3 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
0.20 nM
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High CD22 expression (CD22+++; Median fluorescence=145.0) | ||
Method Description |
To assess the prospect for enhanced cytotoxicity when EmabSN-38 is combined with unconjugated anti-CD20 antibody,cells were co-incubated with veltuzumab (anti-CD20 IgG) and increasing concentrations of EmabSN-38. Humanized RS7 (hRS7) anti-Trop-2 is a nonbinding human IgG1. The test drug was Emab-SN-38 + Vmab (1330 nmol/L).
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In Vitro Model | Burkitt lymphoma | Daudi cells | CVCL_0008 | ||
Experiment 4 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
0.34 nM
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Negative CD22 expression (CD22-; Median fluorescence=7.7) | ||
Method Description |
To assess the prospect for enhanced cytotoxicity when EmabSN-38 is combined with unconjugated anti-CD20 antibody,cells were co-incubated with veltuzumab (anti-CD20 IgG) and increasing concentrations of EmabSN-38. Humanized RS7 (hRS7) anti-Trop-2 is a nonbinding human IgG1. The test drug was Emab-SN-38 + Vmab (1330 nmol/L).
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In Vitro Model | Follicular lymphoma | WSU-FSCCL cells | CVCL_1903 | ||
Experiment 5 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
0.38 nM
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Negative CD22 expression (CD22-; Median fluorescence=7.7) | ||
Method Description |
To assess the prospect for enhanced cytotoxicity when EmabSN-38 is combined with unconjugated anti-CD20 antibody,cells were co-incubated with veltuzumab (anti-CD20 IgG) and increasing concentrations of EmabSN-38. Humanized RS7 (hRS7) anti-Trop-2 is a nonbinding human IgG1. The test drug was Emab-SN-38 alone.
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In Vitro Model | Follicular lymphoma | WSU-FSCCL cells | CVCL_1903 | ||
Experiment 6 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
0.41 nM
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Negative CD22 expression (CD22-; Median fluorescence=7.7) | ||
Method Description |
To assess the prospect for enhanced cytotoxicity when EmabSN-38 is combined with unconjugated anti-CD20 antibody,cells were co-incubated with veltuzumab (anti-CD20 IgG) and increasing concentrations of EmabSN-38. Humanized RS7 (hRS7) anti-Trop-2 is a nonbinding human IgG1. The test drug was Emab-SN-38 + Vmab (133 nmol/L).
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In Vitro Model | Follicular lymphoma | WSU-FSCCL cells | CVCL_1903 | ||
Experiment 7 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
0.46 nM
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Negative CD22 expression (CD22-; Median fluorescence=7.7) | ||
Method Description |
To assess the prospect for enhanced cytotoxicity when EmabSN-38 is combined with unconjugated anti-CD20 antibody,cells were co-incubated with veltuzumab (anti-CD20 IgG) and increasing concentrations of EmabSN-38. Humanized RS7 (hRS7) anti-Trop-2 is a nonbinding human IgG1. The test drug was EmabSN-38 + hRS7 (133 nmol/L).
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In Vitro Model | Follicular lymphoma | WSU-FSCCL cells | CVCL_1903 | ||
Experiment 8 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
0.46 nM
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Negative CD22 expression (CD22-; Median fluorescence=7.7) | ||
Method Description |
To assess the prospect for enhanced cytotoxicity when EmabSN-38 is combined with unconjugated anti-CD20 antibody,cells were co-incubated with veltuzumab (anti-CD20 IgG) and increasing concentrations of EmabSN-38. Humanized RS7 (hRS7) anti-Trop-2 is a nonbinding human IgG1. The test drug was EmabSN-38 + hRS7 (1330 nmol/L).
|
||||
In Vitro Model | Follicular lymphoma | WSU-FSCCL cells | CVCL_1903 | ||
Experiment 9 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
0.50 nM
|
High CD22 expression (CD22+++; Median fluorescence=145.0) | ||
Method Description |
To assess the prospect for enhanced cytotoxicity when EmabSN-38 is combined with unconjugated anti-CD20 antibody,cells were co-incubated with veltuzumab (anti-CD20 IgG) and increasing concentrations of EmabSN-38. Humanized RS7 (hRS7) anti-Trop-2 is a nonbinding human IgG1. The test drug was Emab-SN-38 alone.
|
||||
In Vitro Model | Burkitt lymphoma | Daudi cells | CVCL_0008 | ||
Experiment 10 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
0.51 nM
|
Moderate CD22 expression (CD22++; Median fluorescence=40.8) | ||
Method Description |
To assess the prospect for enhanced cytotoxicity when EmabSN-38 is combined with unconjugated anti-CD20 antibody,cells were co-incubated with veltuzumab (anti-CD20 IgG) and increasing concentrations of EmabSN-38. Humanized RS7 (hRS7) anti-Trop-2 is a nonbinding human IgG1. The test drug was Emab-SN-38 + Vmab (1330 nmol/L).
|
||||
In Vitro Model | Burkitt lymphoma | Ramos cells | CVCL_0597 | ||
Experiment 11 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
0.73 nM
|
Moderate CD22 expression (CD22++; Median fluorescence=40.8) | ||
Method Description |
To assess the prospect for enhanced cytotoxicity when EmabSN-38 is combined with unconjugated anti-CD20 antibody,cells were co-incubated with veltuzumab (anti-CD20 IgG) and increasing concentrations of EmabSN-38. Humanized RS7 (hRS7) anti-Trop-2 is a nonbinding human IgG1. The test drug was Emab-SN-38 + Vmab (133 nmol/L).
|
||||
In Vitro Model | Burkitt lymphoma | Ramos cells | CVCL_0597 | ||
Experiment 12 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
0.81 nM
|
Low CD22 expression (CD22+; Median fluorescence=11.2) | ||
Method Description |
To assess the prospect for enhanced cytotoxicity when EmabSN-38 is combined with unconjugated anti-CD20 antibody,cells were co-incubated with veltuzumab (anti-CD20 IgG) and increasing concentrations of EmabSN-38. Humanized RS7 (hRS7) anti-Trop-2 is a nonbinding human IgG1. The test drug was Emab-SN-38 + Vmab (133 nmol/L).
|
||||
In Vitro Model | Mantle cell lymphoma | JeKo-1 cells | CVCL_1865 | ||
Experiment 13 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
0.83 nM
|
Low CD22 expression (CD22+; Median fluorescence=11.2) | ||
Method Description |
To assess the prospect for enhanced cytotoxicity when EmabSN-38 is combined with unconjugated anti-CD20 antibody,cells were co-incubated with veltuzumab (anti-CD20 IgG) and increasing concentrations of EmabSN-38. Humanized RS7 (hRS7) anti-Trop-2 is a nonbinding human IgG1. The test drug was Emab-SN-38 + Vmab (1330 nmol/L).
|
||||
In Vitro Model | Mantle cell lymphoma | JeKo-1 cells | CVCL_1865 | ||
Experiment 14 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
0.84 nM
|
High CD22 expression (CD22+++; Median fluorescence=145.0) | ||
Method Description |
To assess the prospect for enhanced cytotoxicity when EmabSN-38 is combined with unconjugated anti-CD20 antibody,cells were co-incubated with veltuzumab (anti-CD20 IgG) and increasing concentrations of EmabSN-38. Humanized RS7 (hRS7) anti-Trop-2 is a nonbinding human IgG1. The test drug was EmabSN-38 + hRS7 (133 nmol/L).
|
||||
In Vitro Model | Burkitt lymphoma | Daudi cells | CVCL_0008 | ||
Experiment 15 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
1.16 nM
|
Moderate CD22 expression (CD22++; Median fluorescence=45.9) | ||
Method Description |
To assess the prospect for enhanced cytotoxicity when EmabSN-38 is combined with unconjugated anti-CD20 antibody,cells were co-incubated with veltuzumab (anti-CD20 IgG) and increasing concentrations of EmabSN-38. Humanized RS7 (hRS7) anti-Trop-2 is a nonbinding human IgG1. The test drug was Emab-SN-38 + Vmab (133 nmol/L).
|
||||
In Vitro Model | EBV-related Burkitt lymphoma | Raji cells | CVCL_0511 | ||
Experiment 16 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
1.16 nM
|
Low CD22 expression (CD22+; Median fluorescence=11.2) | ||
Method Description |
To assess the prospect for enhanced cytotoxicity when EmabSN-38 is combined with unconjugated anti-CD20 antibody,cells were co-incubated with veltuzumab (anti-CD20 IgG) and increasing concentrations of EmabSN-38. Humanized RS7 (hRS7) anti-Trop-2 is a nonbinding human IgG1. The test drug was EmabSN-38 + hRS7 (1330 nmol/L).
|
||||
In Vitro Model | Mantle cell lymphoma | JeKo-1 cells | CVCL_1865 | ||
Experiment 17 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
1.50 nM
|
High CD22 expression (CD22+++; Median fluorescence=145.0) | ||
Method Description |
To assess the prospect for enhanced cytotoxicity when EmabSN-38 is combined with unconjugated anti-CD20 antibody,cells were co-incubated with veltuzumab (anti-CD20 IgG) and increasing concentrations of EmabSN-38. Humanized RS7 (hRS7) anti-Trop-2 is a nonbinding human IgG1. The test drug was EmabSN-38 + hRS7 (1330 nmol/L).
|
||||
In Vitro Model | Burkitt lymphoma | Daudi cells | CVCL_0008 | ||
Experiment 18 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
1.66 nM
|
Low CD22 expression (CD22+; Median fluorescence=11.2) | ||
Method Description |
To assess the prospect for enhanced cytotoxicity when EmabSN-38 is combined with unconjugated anti-CD20 antibody,cells were co-incubated with veltuzumab (anti-CD20 IgG) and increasing concentrations of EmabSN-38. Humanized RS7 (hRS7) anti-Trop-2 is a nonbinding human IgG1. The test drug was EmabSN-38 + hRS7 (133 nmol/L).
|
||||
In Vitro Model | Mantle cell lymphoma | JeKo-1 cells | CVCL_1865 | ||
Experiment 19 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
1.72 nM
|
Moderate CD22 expression (CD22++; Median fluorescence=45.9) | ||
Method Description |
To assess the prospect for enhanced cytotoxicity when EmabSN-38 is combined with unconjugated anti-CD20 antibody,cells were co-incubated with veltuzumab (anti-CD20 IgG) and increasing concentrations of EmabSN-38. Humanized RS7 (hRS7) anti-Trop-2 is a nonbinding human IgG1. The test drug was Emab-SN-38 alone.
|
||||
In Vitro Model | EBV-related Burkitt lymphoma | Raji cells | CVCL_0511 | ||
Experiment 20 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
1.77 nM
|
Low CD22 expression (CD22+; Median fluorescence=11.2) | ||
Method Description |
To assess the prospect for enhanced cytotoxicity when EmabSN-38 is combined with unconjugated anti-CD20 antibody,cells were co-incubated with veltuzumab (anti-CD20 IgG) and increasing concentrations of EmabSN-38. Humanized RS7 (hRS7) anti-Trop-2 is a nonbinding human IgG1. The test drug was Emab-SN-38 alone.
|
||||
In Vitro Model | Mantle cell lymphoma | JeKo-1 cells | CVCL_1865 | ||
Experiment 21 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
1.84 nM
|
Moderate CD22 expression (CD22++; Median fluorescence=40.8) | ||
Method Description |
To assess the prospect for enhanced cytotoxicity when EmabSN-38 is combined with unconjugated anti-CD20 antibody,cells were co-incubated with veltuzumab (anti-CD20 IgG) and increasing concentrations of EmabSN-38. Humanized RS7 (hRS7) anti-Trop-2 is a nonbinding human IgG1. The test drug was Emab-SN-38 alone.
|
||||
In Vitro Model | Burkitt lymphoma | Ramos cells | CVCL_0597 | ||
Experiment 22 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
2.21 nM
|
Moderate CD22 expression (CD22++; Median fluorescence=40.8) | ||
Method Description |
To assess the prospect for enhanced cytotoxicity when EmabSN-38 is combined with unconjugated anti-CD20 antibody,cells were co-incubated with veltuzumab (anti-CD20 IgG) and increasing concentrations of EmabSN-38. Humanized RS7 (hRS7) anti-Trop-2 is a nonbinding human IgG1. The test drug was EmabSN-38 + hRS7 (133 nmol/L).
|
||||
In Vitro Model | Burkitt lymphoma | Ramos cells | CVCL_0597 | ||
Experiment 23 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
2.29 nM
|
Moderate CD22 expression (CD22++; Median fluorescence=40.8) | ||
Method Description |
To assess the prospect for enhanced cytotoxicity when EmabSN-38 is combined with unconjugated anti-CD20 antibody,cells were co-incubated with veltuzumab (anti-CD20 IgG) and increasing concentrations of EmabSN-38. Humanized RS7 (hRS7) anti-Trop-2 is a nonbinding human IgG1. The test drug was EmabSN-38 + hRS7 (1330 nmol/L).
|
||||
In Vitro Model | Burkitt lymphoma | Ramos cells | CVCL_0597 | ||
Experiment 24 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
2.45 nM
|
Moderate CD22 expression (CD22++; Median fluorescence=45.9) | ||
Method Description |
To assess the prospect for enhanced cytotoxicity when EmabSN-38 is combined with unconjugated anti-CD20 antibody,cells were co-incubated with veltuzumab (anti-CD20 IgG) and increasing concentrations of EmabSN-38. Humanized RS7 (hRS7) anti-Trop-2 is a nonbinding human IgG1. The test drug was EmabSN-38 + hRS7 (1330 nmol/L).
|
||||
In Vitro Model | EBV-related Burkitt lymphoma | Raji cells | CVCL_0511 | ||
Experiment 25 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
2.88 nM
|
Moderate CD22 expression (CD22++; Median fluorescence=45.9) | ||
Method Description |
To assess the prospect for enhanced cytotoxicity when EmabSN-38 is combined with unconjugated anti-CD20 antibody,cells were co-incubated with veltuzumab (anti-CD20 IgG) and increasing concentrations of EmabSN-38. Humanized RS7 (hRS7) anti-Trop-2 is a nonbinding human IgG1. The test drug was EmabSN-38 + hRS7 (133 nmol/L).
|
||||
In Vitro Model | EBV-related Burkitt lymphoma | Raji cells | CVCL_0511 | ||
Experiment 26 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Effective Concentration (EC50) |
0.52 nM
|
High CD22 expression (CD22+++; Median fluorescence=145.0) | ||
Method Description |
In vitro cytotoxicity by MTS assay of SN-38 and specific Emab anti-CD22SN-38 conjugates against several hematopoietic tumor cell lines.
|
||||
In Vitro Model | Burkitt lymphoma | Daudi cells | CVCL_0008 | ||
Experiment 27 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Effective Concentration (EC50) |
0.68 nM
|
Negative CD22 expression (CD22-; Median fluorescence=7.7) | ||
Method Description |
In vitro cytotoxicity by MTS assay of SN-38 and specific Emab anti-CD22SN-38 conjugates against several hematopoietic tumor cell lines.
|
||||
In Vitro Model | Follicular lymphoma | WSU-FSCCL cells | CVCL_1903 | ||
Experiment 28 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Effective Concentration (EC50) |
1.22 nM
|
Low CD22 expression (CD22+; Median fluorescence=22.9) | ||
Method Description |
In vitro cytotoxicity by MTS assay of SN-38 and specific Emab anti-CD22SN-38 conjugates against several hematopoietic tumor cell lines.
|
||||
In Vitro Model | B acute lymphoblastic leukemia | Reh cells | CVCL_1650 | ||
Experiment 29 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Effective Concentration (EC50) |
1.50 nM
|
Low CD22 expression (CD22+; Median fluorescence=22.9) | ||
Method Description |
In vitro cytotoxicity by MTS assay of SN-38 and specific ADC conjugates against several hematopoietic tumor cell lines. The effect of linkage stability on the cytotoxicity of antibody conjugates as determined by a 4-day MTS assay.
|
||||
In Vitro Model | B acute lymphoblastic leukemia | Reh cells | CVCL_1650 | ||
Experiment 30 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Effective Concentration (EC50) |
1.68 nM
|
Low CD22 expression (CD22+; Median fluorescence=22.9) | ||
Method Description |
In vitro cytotoxicity by MTS assay of SN-38 and specific Emab anti-CD22SN-38 conjugates against several hematopoietic tumor cell lines.
|
||||
In Vitro Model | Adult B acute lymphoblastic leukemia | RS4;11 cells | CVCL_0093 | ||
Experiment 31 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Effective Concentration (EC50) |
2.10 nM
|
Moderate CD22 expression (CD22++; Median fluorescence=45.9) | ||
Method Description |
In vitro cytotoxicity by MTS assay of SN-38 and specific Emab anti-CD22SN-38 conjugates against several hematopoietic tumor cell lines.
|
||||
In Vitro Model | EBV-related Burkitt lymphoma | Raji cells | CVCL_0511 | ||
Experiment 32 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Effective Concentration (EC50) |
2.25 nM
|
Low CD22 expression (CD22+; Median fluorescence=11.2) | ||
Method Description |
In vitro cytotoxicity by MTS assay of SN-38 and specific Emab anti-CD22SN-38 conjugates against several hematopoietic tumor cell lines.
|
||||
In Vitro Model | Mantle cell lymphoma | JeKo-1 cells | CVCL_1865 | ||
Experiment 33 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Effective Concentration (EC50) |
2.67 nM
|
Low CD22 expression (CD22+; Median fluorescence=16.0) | ||
Method Description |
In vitro cytotoxicity by MTS assay of SN-38 and specific Emab anti-CD22SN-38 conjugates against several hematopoietic tumor cell lines.
|
||||
In Vitro Model | Childhood B acute lymphoblastic leukemia | 697 cells | CVCL_0079 | ||
Experiment 34 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Effective Concentration (EC50) |
2.70 nM
|
Moderate CD22 expression (CD22++; Median fluorescence=40.8) | ||
Method Description |
In vitro cytotoxicity by MTS assay of SN-38 and specific ADC conjugates against several hematopoietic tumor cell lines. The effect of linkage stability on the cytotoxicity of antibody conjugates as determined by a 4-day MTS assay.
|
||||
In Vitro Model | Burkitt lymphoma | Ramos cells | CVCL_0597 | ||
Experiment 35 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Effective Concentration (EC50) |
2.92 nM
|
Moderate CD22 expression (CD22++; Median fluorescence=40.8) | ||
Method Description |
In vitro cytotoxicity by MTS assay of SN-38 and specific Emab anti-CD22SN-38 conjugates against several hematopoietic tumor cell lines.
|
||||
In Vitro Model | Burkitt lymphoma | Ramos cells | CVCL_0597 | ||
Experiment 36 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Effective Concentration (EC50) |
3.20 nM
|
Moderate CD22 expression (CD22++; Median fluorescence=45.9) | ||
Method Description |
In vitro cytotoxicity by MTS assay of SN-38 and specific ADC conjugates against several hematopoietic tumor cell lines. The effect of linkage stability on the cytotoxicity of antibody conjugates as determined by a 4-day MTS assay.
|
||||
In Vitro Model | EBV-related Burkitt lymphoma | Raji cells | CVCL_0511 | ||
Experiment 37 Reporting the Activity Date of This ADC | [18] | ||||
Efficacy Data | Half Maximal Effective Concentration (EC50) |
3.65 nM
|
Low CD205 expression (CD205+; IHC 1+) | ||
Method Description |
In vitro cytotoxicity by MTS assay of SN-38 and specific Emab anti-CD22SN-38 conjugates against several hematopoietic tumor cell lines.
|
||||
In Vitro Model | Burkitt lymphoma | MN-60 cells | CVCL_1421 |
M603-SN38 DAR6 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Experiment 1 Reporting the Activity Date of This ADC | [19] | ||||
Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 0.00% (Day 25) | High 5T4 expression (5T4+++) | ||
Method Description |
Treated with m603.
|
||||
In Vivo Model | Pancreatic cancer CDX model | ||||
In Vitro Model | Pancreatic cancer | Pancreatic cancer cells | Homo sapiens | ||
Experiment 2 Reporting the Activity Date of This ADC | [19] | ||||
Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 37.83% (Day 25) | High 5T4 expression (5T4+++) | ||
Method Description |
Treated with m603-SN38.
|
||||
In Vivo Model | Pancreatic cancer CDX model | ||||
In Vitro Model | Pancreatic cancer | Pancreatic cancer cells | Homo sapiens |
Revealed Based on the Cell Line Data
Experiment 1 Reporting the Activity Date of This ADC | [19] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
3.90 nM
|
High 5T4 expression (5T4+++) | ||
Method Description |
Cells in the logarithmic phase of growth were collected and seeded in 96-well plates at a density of 510 3 cells/well and cultured overnight. The culture medium was removed and serial dilution ADCs or naked antibodies were added into the wells of 96-well plates in 200 L medium.
|
||||
In Vitro Model | Pancreatic ductal adenocarcinoma | BxPC-3 cells | CVCL_0186 | ||
Experiment 2 Reporting the Activity Date of This ADC | [19] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
244.20 nM
|
Moderate 5T4 expression (5T4++) | ||
Method Description |
Cells in the logarithmic phase of growth were collected and seeded in 96-well plates at a density of 510 3 cells/well and cultured overnight. The culture medium was removed and serial dilution ADCs or naked antibodies were added into the wells of 96-well plates in 200 L medium.
|
||||
In Vitro Model | Adult hepatocellular carcinoma | Huh-7 cells | CVCL_0336 |
N501-SN38 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Experiment 1 Reporting the Activity Date of This ADC | [19] | ||||
Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 0.00% (Day 25) | High 5T4 expression (5T4+++) | ||
Method Description |
Treated with n501.
|
||||
In Vivo Model | Pancreatic cancer CDX model | ||||
In Vitro Model | Pancreatic cancer | Pancreatic cancer cells | Homo sapiens | ||
Experiment 2 Reporting the Activity Date of This ADC | [19] | ||||
Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 62.93% (Day 25) | High 5T4 expression (5T4+++) | ||
Method Description |
Treated with n501-SN38.
|
||||
In Vivo Model | Pancreatic cancer CDX model | ||||
In Vitro Model | Pancreatic cancer | Pancreatic cancer cells | Homo sapiens |
Revealed Based on the Cell Line Data
Experiment 1 Reporting the Activity Date of This ADC | [19] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
11.90 nM
|
High 5T4 expression (5T4+++) | ||
Method Description |
Cells in the logarithmic phase of growth were collected and seeded in 96-well plates at a density of 510 3 cells/well and cultured overnight. The culture medium was removed and serial dilution ADCs or naked antibodies were added into the wells of 96-well plates in 200 L medium.
|
||||
In Vitro Model | Pancreatic ductal adenocarcinoma | BxPC-3 cells | CVCL_0186 | ||
Experiment 2 Reporting the Activity Date of This ADC | [19] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
49.80 nM
|
Moderate 5T4 expression (5T4++) | ||
Method Description |
Cells in the logarithmic phase of growth were collected and seeded in 96-well plates at a density of 510 3 cells/well and cultured overnight. The culture medium was removed and serial dilution ADCs or naked antibodies were added into the wells of 96-well plates in 200 L medium.
|
||||
In Vitro Model | Adult hepatocellular carcinoma | Huh-7 cells | CVCL_0336 |
Anti-BCMA R347-SG3249 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Experiment 1 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 16.02% (Day 21) | Moderate BCMA expression (BCMA++) | ||
Method Description |
Mice were treated with either a single intravenous dose of ADCs at 1 mg/kg, or dosed intravenously with J6M0-mc-MMAF ADC weekly at a dose of 1 mg/kg for 3 weeks. Control mice were left untreated.
|
||||
In Vivo Model | JJN-3 CDX model | ||||
In Vitro Model | Plasma cell myeloma | JJN-3 cells | CVCL_2078 |
CAC10-GT [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Experiment 1 Reporting the Activity Date of This ADC | [21] | ||||
Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 67.00% (Day 28) | Positive CD30 expression (CD30+++/++) | ||
Method Description |
Tumor cells, as suspensions, were implanted subcutaneously in SCID or nude mice. Upon tumor engraftment, mice were randomized to study groups (5 mice per group) when the average tumor volume reached about 100 mm3. The ADC or vehicle controls were dosed once via intraperitoneal injection. The dose of cAC10-GT=10 mg/kg.
|
||||
In Vivo Model | HD CDX model | ||||
In Vitro Model | Hodgkin's disease | L540cy cells | Homo sapiens | ||
Experiment 2 Reporting the Activity Date of This ADC | [21] | ||||
Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 67.00% (Day 28) | Positive CD30 expression (CD30+++/++) | ||
Method Description |
Tumor cells, as suspensions, were implanted subcutaneously in SCID or nude mice. Upon tumor engraftment, mice were randomized to study groups (5 mice per group) when the average tumor volume reached about 100 mm3. The ADC or vehicle controls were dosed once via intraperitoneal injection. The dose of cAC10-GT=30mg/kg.
|
||||
In Vivo Model | HD CDX model | ||||
In Vitro Model | Hodgkin's disease | L540cy cells | Homo sapiens | ||
Experiment 3 Reporting the Activity Date of This ADC | [21] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
20.00 ng/mL
|
High CD30 expression (CD30+++; 285,000 CD30 molecules/cell) | ||
Method Description |
Serial dilutions of ADCs in cell culture media were prepared at 4x working concentrations, and 50 uL of each dilution was added to the 96-well plates. Following addition of test articles, cells were incubated for 4 days at 37°C, after which growth inhibition was assessed by the addition of CellTiter-Glo and luminescence was measured on a plate reader.
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|
||||
In Vitro Model | Precursor T-cell acute lymphoblastic leukemia | ALCL cells | CVCL_A036 | ||
Experiment 4 Reporting the Activity Date of This ADC | [21] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
27.00 ng/mL
|
High CD30 expression (CD30+++; 180,000 CD30 molecules/cell) | ||
Method Description |
Serial dilutions of ADCs in cell culture media were prepared at 4x working concentrations, and 50 uL of each dilution was added to the 96-well plates. Following addition of test articles, cells were incubated for 4 days at 37°C, after which growth inhibition was assessed by the addition of CellTiter-Glo and luminescence was measured on a plate reader.
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|
||||
In Vitro Model | Anaplastic large cell lymphoma | DEL/BVR cells | CVCL_1170 | ||
Experiment 5 Reporting the Activity Date of This ADC | [21] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
79.00 ng/mL
|
High CD30 expression (CD30+++; 400,000 CD30 molecules/cell) | ||
Method Description |
Serial dilutions of ADCs in cell culture media were prepared at 4x working concentrations, and 50 uL of each dilution was added to the 96-well plates. Following addition of test articles, cells were incubated for 4 days at 37°C, after which growth inhibition was assessed by the addition of CellTiter-Glo and luminescence was measured on a plate reader.
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|
||||
In Vitro Model | Hodgkin's disease | L540cy cells | Homo sapiens | ||
Experiment 6 Reporting the Activity Date of This ADC | [21] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
160.00 ng/mL
|
High CD30 expression (CD30+++; 320,000 CD30 molecules/cell) | ||
Method Description |
Serial dilutions of ADCs in cell culture media were prepared at 4x working concentrations, and 50 uL of each dilution was added to the 96-well plates. Following addition of test articles, cells were incubated for 4 days at 37°C, after which growth inhibition was assessed by the addition of CellTiter-Glo and luminescence was measured on a plate reader.
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|
||||
In Vitro Model | ALK-positive anaplastic large cell lymphoma | Karpas-299 cells | CVCL_1324 | ||
Experiment 7 Reporting the Activity Date of This ADC | [21] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
850.00 ng/mL
|
Low CD30 expression (CD30+; 70,000 CD30 molecules/cell) | ||
Method Description |
Serial dilutions of ADCs in cell culture media were prepared at 4x working concentrations, and 50 uL of each dilution was added to the 96-well plates. Following addition of test articles, cells were incubated for 4 days at 37°C, after which growth inhibition was assessed by the addition of CellTiter-Glo and luminescence was measured on a plate reader.
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|
||||
In Vitro Model | Hodgkin lymphoma | L-428 cells | CVCL_1361 |
Anti-BCMA I09-SG3249 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Experiment 1 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 94.55% (Day 21) | High BCMA expression (BCMA+++) | ||
Method Description |
Mice were treated with either a single intravenous dose of the ADCs at 0.3 mg/kg or dosed intravenously with J6M0-mc-MMAFweekly at a dose of 0.3 mg/kg for 2 weeks.
|
||||
In Vivo Model | NCI-H929 CDX model | ||||
In Vitro Model | Plasma cell myeloma | NCI-H929 cells | CVCL_1600 | ||
Experiment 2 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 95.16% (Day 21) | Moderate BCMA expression (BCMA++) | ||
Method Description |
Mice were treated with either a single intravenous dose of ADCs at 1 mg/kg, or dosed intravenously with J6M0-mc-MMAF ADC weekly at a dose of 1 mg/kg for 3 weeks. Control mice were left untreated.
|
||||
In Vivo Model | JJN-3 CDX model | ||||
In Vitro Model | Plasma cell myeloma | JJN-3 cells | CVCL_2078 | ||
Experiment 3 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 96.37% (Day 32) | Moderate BCMA expression (BCMA++) | ||
Method Description |
Mice were treated with either a single intravenous dose of ADCs at 1 mg/kg, or dosed intravenously with J6M0-mc-MMAF ADC weekly at a dose of 1 mg/kg for 4 weeks. Control mice were left untreated.
|
||||
In Vivo Model | MM.1S CDX model | ||||
In Vitro Model | Plasma cell myeloma | MM1.S cells | CVCL_8792 |
Revealed Based on the Cell Line Data
Experiment 1 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
2.81 nM
|
Moderate BCMA expression (BCMA++) | ||
Method Description |
The ability of the ADCs to kill multiple myeloma cells in vitro inthe presence of soluble BCMA (sBCMA, 0 ng/ml) as compared to the 09-SG3249 ADC was evaluated in MM.1S cells, except that tested cell lines also were treated with BCMA-containing conditioned media collected from Ad293 cells expressing human BCMA.
|
||||
In Vitro Model | Plasma cell myeloma | MM1.S cells | CVCL_8792 | ||
Experiment 2 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
5.55 nM
|
Moderate BCMA expression (BCMA++) | ||
Method Description |
The ability of the ADCs to kill multiple myeloma cells in vitro inthe presence of soluble BCMA (sBCMA, 270 ng/ml) as compared to the 09-SG3249 ADC was evaluated in MM.1S cells, except that tested cell lines also were treated with BCMA-containing conditioned media collected from Ad293 cells expressing human BCMA.
|
||||
In Vitro Model | Plasma cell myeloma | MM1.S cells | CVCL_8792 | ||
Experiment 3 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
7.79 nM
|
Moderate BCMA expression (BCMA++) | ||
Method Description |
The ability of the ADCs to kill multiple myeloma cells in vitro inthe presence of soluble BCMA (sBCMA, 75 ng/ml) as compared to the 09-SG3249 ADC was evaluated in MM.1S cells, except that tested cell lines also were treated with BCMA-containing conditioned media collected from Ad293 cells expressing human BCMA.
|
||||
In Vitro Model | Plasma cell myeloma | MM1.S cells | CVCL_8792 | ||
Experiment 4 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
16.16 nM
|
Moderate BCMA expression (BCMA++) | ||
Method Description |
The ability of the ADCs to kill multiple myeloma cells in vitro inthe presence of soluble BCMA (sBCMA, 720 ng/ml) as compared to the 09-SG3249 ADC was evaluated in MM.1S cells, except that tested cell lines also were treated with BCMA-containing conditioned media collected from Ad293 cells expressing human BCMA.
|
||||
In Vitro Model | Plasma cell myeloma | MM1.S cells | CVCL_8792 |
Anti-BCMA L15-SG3249 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Experiment 1 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 95.16% (Day 21) | Moderate BCMA expression (BCMA++) | ||
Method Description |
Mice were treated with either a single intravenous dose of ADCs at 1 mg/kg, or dosed intravenously with J6M0-mc-MMAF ADC weekly at a dose of 1 mg/kg for 3 weeks. Control mice were left untreated.
|
||||
In Vivo Model | JJN-3 CDX model | ||||
In Vitro Model | Plasma cell myeloma | JJN-3 cells | CVCL_2078 | ||
Experiment 2 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 96.37% (Day 32) | Moderate BCMA expression (BCMA++) | ||
Method Description |
Mice were treated with either a single intravenous dose of ADCs at 1 mg/kg, or dosed intravenously with J6M0-mc-MMAF ADC weekly at a dose of 1 mg/kg for 4 weeks. Control mice were left untreated.
|
||||
In Vivo Model | MM.1S CDX model | ||||
In Vitro Model | Plasma cell myeloma | MM1.S cells | CVCL_8792 | ||
Experiment 3 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 97.35% (Day 21) | High BCMA expression (BCMA+++) | ||
Method Description |
Mice were treated with either a single intravenous dose of the ADCs at 0.3 mg/kg or dosed intravenously with J6M0-mc-MMAFweekly at a dose of 0.3 mg/kg for 2 weeks.
|
||||
In Vivo Model | NCI-H929 CDX model | ||||
In Vitro Model | Plasma cell myeloma | NCI-H929 cells | CVCL_1600 |
Anti-BCMA 15B2WT-SG3249 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Experiment 1 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 95.59% (Day 21) | High BCMA expression (BCMA+++) | ||
Method Description |
Mice were treated with either a single intravenous dose of the ADCs at 0.3 mg/kg or dosed intravenously with J6M0-mc-MMAFweekly at a dose of 0.3 mg/kg for 2 weeks.
|
||||
In Vivo Model | NCI-H929 CDX model | ||||
In Vitro Model | Plasma cell myeloma | NCI-H929 cells | CVCL_1600 |
Anti-BCMA 15B2GL-SG3249 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Experiment 1 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 96.37% (Day 32) | Moderate BCMA expression (BCMA++) | ||
Method Description |
Mice were treated with either a single intravenous dose of ADCs at 1 mg/kg, or dosed intravenously with J6M0-mc-MMAF ADC weekly at a dose of 1 mg/kg for 4 weeks. Control mice were left untreated.
|
||||
In Vivo Model | MM.1S CDX model | ||||
In Vitro Model | Plasma cell myeloma | MM1.S cells | CVCL_8792 | ||
Experiment 2 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 98.73% (Day 35) | High BCMA expression (BCMA+++) | ||
Method Description |
Mice were treated with either a single intravenous dose of ADCs at 1 mg/kg, or dosed intravenously with J6M0-mc-MMAF ADC weekly at a dose of 3 mg/kg for 4 weeks. Control mice were left untreated.
|
||||
In Vivo Model | MM.1R CDX model | ||||
In Vitro Model | Plasma cell myeloma | MM1.R cells | CVCL_8794 |
Revealed Based on the Cell Line Data
Experiment 1 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
5.99 nM
|
High BCMA expression (BCMA+++) | ||
Method Description |
Treatments were then serially diluted 1:3 in RPMI+10% FBS. 20uL of this series was added to the cells in duplicate, resulting in a 12-point dose curve of antibody-drug conjugate and media-only controls also were included. Plates were incubated at 37°C, 5% CO for 9 hours.
|
||||
In Vitro Model | Plasma cell myeloma | NCI-H929 cells | CVCL_1600 | ||
Experiment 2 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
8.64 nM
|
High BCMA expression (BCMA+++) | ||
Method Description |
Treatments were then serially diluted 1:3 in RPMI+10% FBS. 20uL of this series was added to the cells in duplicate, resulting in a 12-point dose curve of antibody-drug conjugate and media-only controls also were included. Plates were incubated at 37°C, 5% CO for 9 hours.
|
||||
In Vitro Model | Plasma cell myeloma | MM1.R cells | CVCL_8794 | ||
Experiment 3 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
14.47 nM
|
Moderate BCMA expression (BCMA++) | ||
Method Description |
The ability of the ADCs to kill multiple myeloma cells in vitro inthe presence of soluble BCMA (sBCMA, 0 ng/ml) as compared to the 09-SG3249 ADC was evaluated in MM.1S cells, except that tested cell lines also were treated with BCMA-containing conditioned media collected from Ad293 cells expressing human BCMA.
|
||||
In Vitro Model | Plasma cell myeloma | MM1.S cells | CVCL_8792 | ||
Experiment 4 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
16.09 nM
|
Moderate BCMA expression (BCMA++) | ||
Method Description |
The ability of the ADCs to kill multiple myeloma cells in vitro inthe presence of soluble BCMA (sBCMA, 75 ng/ml) as compared to the 09-SG3249 ADC was evaluated in MM.1S cells, except that tested cell lines also were treated with BCMA-containing conditioned media collected from Ad293 cells expressing human BCMA.
|
||||
In Vitro Model | Plasma cell myeloma | MM1.S cells | CVCL_8792 | ||
Experiment 5 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
16.80 nM
|
Moderate BCMA expression (BCMA++) | ||
Method Description |
Treatments were then serially diluted 1:3 in RPMI+10% FBS. 20uL of this series was added to the cells in duplicate, resulting in a 12-point dose curve of antibody-drug conjugate and media-only controls also were included. Plates were incubated at 37°C, 5% CO for 9 hours.
|
||||
In Vitro Model | Plasma cell myeloma | MM1.S cells | CVCL_8792 | ||
Experiment 6 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
22.86 nM
|
Moderate BCMA expression (BCMA++) | ||
Method Description |
The ability of the ADCs to kill multiple myeloma cells in vitro inthe presence of soluble BCMA (sBCMA, 270 ng/ml) as compared to the 09-SG3249 ADC was evaluated in MM.1S cells, except that tested cell lines also were treated with BCMA-containing conditioned media collected from Ad293 cells expressing human BCMA.
|
||||
In Vitro Model | Plasma cell myeloma | MM1.S cells | CVCL_8792 | ||
Experiment 7 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
29.12 nM
|
Moderate BCMA expression (BCMA++) | ||
Method Description |
The ability of the ADCs to kill multiple myeloma cells in vitro inthe presence of soluble BCMA (sBCMA, 720 ng/ml) as compared to the 09-SG3249 ADC was evaluated in MM.1S cells, except that tested cell lines also were treated with BCMA-containing conditioned media collected from Ad293 cells expressing human BCMA.
|
||||
In Vitro Model | Plasma cell myeloma | MM1.S cells | CVCL_8792 | ||
Experiment 8 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
31.40 nM
|
Low BCMA expression (BCMA+) | ||
Method Description |
Treatments were then serially diluted 1:3 in RPMI+10% FBS. 20uL of this series was added to the cells in duplicate, resulting in a 12-point dose curve of antibody-drug conjugate and media-only controls also were included. Plates were incubated at 37°C, 5% CO for 9 hours.
|
||||
In Vitro Model | Plasma cell myeloma | L-363 cells | CVCL_1357 | ||
Experiment 9 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
36.28 nM
|
Moderate BCMA expression (BCMA++) | ||
Method Description |
Treatments were then serially diluted 1:3 in RPMI+10% FBS. 20uL of this series was added to the cells in duplicate, resulting in a 12-point dose curve of antibody-drug conjugate and media-only controls also were included. Plates were incubated at 37°C, 5% CO for 9 hours.
|
||||
In Vitro Model | Plasma cell myeloma | JJN-3 cells | CVCL_2078 | ||
Experiment 10 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
39.00 nM
|
Moderate BCMA expression (BCMA++) | ||
Method Description |
Treatments were then serially diluted 1:3 in RPMI+10% FBS. 20uL of this series was added to the cells in duplicate, resulting in a 12-point dose curve of antibody-drug conjugate and media-only controls also were included. Plates were incubated at 37°C, 5% CO for 9 hours.
|
||||
In Vitro Model | Plasma cell myeloma | U266B1 cells | CVCL_0566 | ||
Experiment 11 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
153.00 nM
|
High BCMA expression (BCMA+++) | ||
Method Description |
Treatments were then serially diluted 1:3 in RPMI+10% FBS. 20uL of this series was added to the cells in duplicate, resulting in a 12-point dose curve of antibody-drug conjugate and media-only controls also were included. Plates were incubated at 37°C, 5% CO for 9 hours.
|
||||
In Vitro Model | Plasma cell myeloma | EJM cells | CVCL_2030 | ||
Experiment 12 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
201.00 nM
|
Moderate BCMA expression (BCMA++) | ||
Method Description |
Treatments were then serially diluted 1:3 in RPMI+10% FBS. 20uL of this series was added to the cells in duplicate, resulting in a 12-point dose curve of antibody-drug conjugate and media-only controls also were included. Plates were incubated at 37°C, 5% CO for 9 hours.
|
||||
In Vitro Model | Plasma cell myeloma | OPM-2 cells | CVCL_1625 | ||
Experiment 13 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | > 500.00 nM | Negative BCMA expression (BCMA-) | ||
Method Description |
Treatments were then serially diluted 1:3 in RPMI+10% FBS. 20uL of this series was added to the cells in duplicate, resulting in a 12-point dose curve of antibody-drug conjugate and media-only controls also were included. Plates were incubated at 37°C, 5% CO for 9 hours.
|
||||
In Vitro Model | EBV-related Burkitt lymphoma | Raji cells | CVCL_0511 | ||
Experiment 14 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | > 500.00 nM | Negative BCMA expression (BCMA-) | ||
Method Description |
Treatments were then serially diluted 1:3 in RPMI+10% FBS. 20uL of this series was added to the cells in duplicate, resulting in a 12-point dose curve of antibody-drug conjugate and media-only controls also were included. Plates were incubated at 37°C, 5% CO for 9 hours.
|
||||
In Vitro Model | T acute lymphoblastic leukemia | Jurkat cells | CVCL_0065 |
H00-GT [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Experiment 1 Reporting the Activity Date of This ADC | [21] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
19.00 ng/mL
|
High CD30 expression (CD30+++; 285,000 CD30 molecules/cell) | ||
Method Description |
Serial dilutions of ADCs in cell culture media were prepared at 4x working concentrations, and 50 uL of each dilution was added to the 96-well plates. Following addition of test articles, cells were incubated for 4 days at 37°C, after which growth inhibition was assessed by the addition of CellTiter-Glo and luminescence was measured on a plate reader.
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|
||||
In Vitro Model | Precursor T-cell acute lymphoblastic leukemia | ALCL cells | CVCL_A036 | ||
Experiment 2 Reporting the Activity Date of This ADC | [21] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
25.00 ng/mL
|
High CD30 expression (CD30+++; 180,000 CD30 molecules/cell) | ||
Method Description |
Serial dilutions of ADCs in cell culture media were prepared at 4x working concentrations, and 50 uL of each dilution was added to the 96-well plates. Following addition of test articles, cells were incubated for 4 days at 37°C, after which growth inhibition was assessed by the addition of CellTiter-Glo and luminescence was measured on a plate reader.
Click to Show/Hide
|
||||
In Vitro Model | Anaplastic large cell lymphoma | DEL/BVR cells | CVCL_1170 | ||
Experiment 3 Reporting the Activity Date of This ADC | [21] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
46.00 ng/mL
|
High CD30 expression (CD30+++; 400,000 CD30 molecules/cell) | ||
Method Description |
Serial dilutions of ADCs in cell culture media were prepared at 4x working concentrations, and 50 uL of each dilution was added to the 96-well plates. Following addition of test articles, cells were incubated for 4 days at 37°C, after which growth inhibition was assessed by the addition of CellTiter-Glo and luminescence was measured on a plate reader.
Click to Show/Hide
|
||||
In Vitro Model | Hodgkin's disease | L540cy cells | Homo sapiens | ||
Experiment 4 Reporting the Activity Date of This ADC | [21] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
160.00 ng/mL
|
High CD30 expression (CD30+++; 320,000 CD30 molecules/cell) | ||
Method Description |
Serial dilutions of ADCs in cell culture media were prepared at 4x working concentrations, and 50 uL of each dilution was added to the 96-well plates. Following addition of test articles, cells were incubated for 4 days at 37°C, after which growth inhibition was assessed by the addition of CellTiter-Glo and luminescence was measured on a plate reader.
Click to Show/Hide
|
||||
In Vitro Model | ALK-positive anaplastic large cell lymphoma | Karpas-299 cells | CVCL_1324 | ||
Experiment 5 Reporting the Activity Date of This ADC | [21] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
820.00 ng/mL
|
Low CD30 expression (CD30+; 70,000 CD30 molecules/cell) | ||
Method Description |
Serial dilutions of ADCs in cell culture media were prepared at 4x working concentrations, and 50 uL of each dilution was added to the 96-well plates. Following addition of test articles, cells were incubated for 4 days at 37°C, after which growth inhibition was assessed by the addition of CellTiter-Glo and luminescence was measured on a plate reader.
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|
||||
In Vitro Model | Hodgkin lymphoma | L-428 cells | CVCL_1361 |
Anti-BCMA J6M0-SG3249 [Investigative]
Revealed Based on the Cell Line Data
Experiment 1 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
4.82 nM
|
Moderate BCMA expression (BCMA++) | ||
Method Description |
The ability of the ADCs to kill multiple myeloma cells in vitro inthe presence of soluble BCMA (sBCMA, 0 ng/ml) as compared to the 09-SG3249 ADC was evaluated in MM.1S cells, except that tested cell lines also were treated with BCMA-containing conditioned media collected from Ad293 cells expressing human BCMA.
|
||||
In Vitro Model | Plasma cell myeloma | MM1.S cells | CVCL_8792 | ||
Experiment 2 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
12.83 nM
|
Moderate BCMA expression (BCMA++) | ||
Method Description |
The ability of the ADCs to kill multiple myeloma cells in vitro inthe presence of soluble BCMA (sBCMA, 75 ng/ml) as compared to the 09-SG3249 ADC was evaluated in MM.1S cells, except that tested cell lines also were treated with BCMA-containing conditioned media collected from Ad293 cells expressing human BCMA.
|
||||
In Vitro Model | Plasma cell myeloma | MM1.S cells | CVCL_8792 | ||
Experiment 3 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
32.26 nM
|
Moderate BCMA expression (BCMA++) | ||
Method Description |
The ability of the ADCs to kill multiple myeloma cells in vitro inthe presence of soluble BCMA (sBCMA, 270 ng/ml) as compared to the 09-SG3249 ADC was evaluated in MM.1S cells, except that tested cell lines also were treated with BCMA-containing conditioned media collected from Ad293 cells expressing human BCMA.
|
||||
In Vitro Model | Plasma cell myeloma | MM1.S cells | CVCL_8792 | ||
Experiment 4 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
92.92 nM
|
Moderate BCMA expression (BCMA++) | ||
Method Description |
The ability of the ADCs to kill multiple myeloma cells in vitro inthe presence of soluble BCMA (sBCMA, 720 ng/ml) as compared to the 09-SG3249 ADC was evaluated in MM.1S cells, except that tested cell lines also were treated with BCMA-containing conditioned media collected from Ad293 cells expressing human BCMA.
|
||||
In Vitro Model | Plasma cell myeloma | MM1.S cells | CVCL_8792 |
40H3-CL2A-SN38 [Investigative]
Revealed Based on the Cell Line Data
Experiment 1 Reporting the Activity Date of This ADC | [22] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
19.71 nM
|
High EGFR expression (EGFR+++) | ||
Method Description |
1 x104 cells per well in a volume of 100 ul were plated in 96-well tissue culture plates. After 24 h, ADCs were added at the indicated concentrations. After 72 h, the medium was removed and the viability was determined using the CellTiter-Glo luminescent cell viability assay kit.
|
||||
In Vitro Model | Skin squamous cell carcinoma | A431 cells | CVCL_0037 | ||
Experiment 2 Reporting the Activity Date of This ADC | [22] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
27.83 nM
|
High EGFR expression (EGFR+++) | ||
Method Description |
1 x104 cells per well in a volume of 100 ul were plated in 96-well tissue culture plates. After 24 h, ADCs were added at the indicated concentrations. After 72 h, the medium was removed and the viability was determined using the CellTiter-Glo luminescent cell viability assay kit.
|
||||
In Vitro Model | Breast adenocarcinoma | MDA-MB-468 cells | CVCL_0419 | ||
Experiment 3 Reporting the Activity Date of This ADC | [22] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
98.81 nM
|
Moderate EGFR expression (EGFR++) | ||
Method Description |
1 x104 cells per well in a volume of 100 ul were plated in 96-well tissue culture plates. After 24 h, ADCs were added at the indicated concentrations. After 72 h, the medium was removed and the viability was determined using the CellTiter-Glo luminescent cell viability assay kit.
|
||||
In Vitro Model | Invasive breast carcinoma of no special type | BT-20 cells | CVCL_0178 | ||
Experiment 4 Reporting the Activity Date of This ADC | [22] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | > 100.00 nM | Negative EGFR expression (EGFR-) | ||
Method Description |
1 x104 cells per well in a volume of 100 ul were plated in 96-well tissue culture plates. After 24 h, ADCs were added at the indicated concentrations. After 72 h, the medium was removed and the viability was determined using the CellTiter-Glo luminescent cell viability assay kit.
|
||||
In Vitro Model | Breast adenocarcinoma | MDA-MB-231 cells | CVCL_0062 |
Veltuzumab-SN-38 [Investigative]
Revealed Based on the Cell Line Data
Experiment 1 Reporting the Activity Date of This ADC | [23] | ||||
Efficacy Data | Half Maximal Effective Concentration (EC50) |
0.83 nM
|
Moderate CD20 expression (CD20++) | ||
Method Description |
Cytotoxicity was determined using the MTS dye reduction assay.
|
||||
In Vitro Model | Follicular lymphoma | WSU-FSCCL cells | CVCL_1903 | ||
Experiment 2 Reporting the Activity Date of This ADC | [23] | ||||
Efficacy Data | Half Maximal Effective Concentration (EC50) |
1.98 nM
|
High CD20 expression (CD20+++) | ||
Method Description |
Cytotoxicity was determined using the MTS dye reduction assay.
|
||||
In Vitro Model | Mantle cell lymphoma | JeKo-1 cells | CVCL_1865 | ||
Experiment 3 Reporting the Activity Date of This ADC | [23] | ||||
Efficacy Data | Half Maximal Effective Concentration (EC50) |
4.88 nM
|
High CD20 expression (CD20+++) | ||
Method Description |
Cytotoxicity was determined using the MTS dye reduction assay.
|
||||
In Vitro Model | EBV-related Burkitt lymphoma | Raji cells | CVCL_0511 | ||
Experiment 4 Reporting the Activity Date of This ADC | [23] | ||||
Efficacy Data | Half Maximal Effective Concentration (EC50) |
13.56 nM
|
High CD20 expression (CD20+++) | ||
Method Description |
Cytotoxicity was determined using the MTS dye reduction assay.
|
||||
In Vitro Model | Burkitt lymphoma | Daudi cells | CVCL_0008 | ||
Experiment 5 Reporting the Activity Date of This ADC | [23] | ||||
Efficacy Data | Half Maximal Effective Concentration (EC50) | > 50.00 nM | High CD20 expression (CD20+++) | ||
Method Description |
Cytotoxicity was determined using the MTS dye reduction assay.
|
||||
In Vitro Model | Burkitt lymphoma | Ramos cells | CVCL_0597 | ||
Experiment 6 Reporting the Activity Date of This ADC | [23] | ||||
Efficacy Data | Half Maximal Effective Concentration (EC50) | > 50.00 nM | Low CD20 expression (CD20+) | ||
Method Description |
Cytotoxicity was determined using the MTS dye reduction assay.
|
||||
In Vitro Model | B acute lymphoblastic leukemia | Reh cells | CVCL_1650 | ||
Experiment 7 Reporting the Activity Date of This ADC | [23] | ||||
Efficacy Data | Half Maximal Effective Concentration (EC50) | > 50.00 nM | Low CD20 expression (CD20+) | ||
Method Description |
Cytotoxicity was determined using the MTS dye reduction assay.
|
||||
In Vitro Model | Childhood B acute lymphoblastic leukemia | 697 cells | CVCL_0079 | ||
Experiment 8 Reporting the Activity Date of This ADC | [23] | ||||
Efficacy Data | Half Maximal Effective Concentration (EC50) | > 50.00 nM | Low CD20 expression (CD20+) | ||
Method Description |
Cytotoxicity was determined using the MTS dye reduction assay.
|
||||
In Vitro Model | Adult B acute lymphoblastic leukemia | RS4;11 cells | CVCL_0093 | ||
Experiment 9 Reporting the Activity Date of This ADC | [23] | ||||
Efficacy Data | Half Maximal Effective Concentration (EC50) | > 50.00 nM | Low CD20 expression (CD20+) | ||
Method Description |
Cytotoxicity was determined using the MTS dye reduction assay.
|
||||
In Vitro Model | Burkitt lymphoma | MN-60 cells | CVCL_1421 | ||
Experiment 10 Reporting the Activity Date of This ADC | [23] | ||||
Efficacy Data | Half Maximal Effective Concentration (EC50) |
77.90 nM
|
Moderate CD22 expression (CD22++) | ||
Method Description |
Cytotoxicity was determined using the MTS dye reduction assay.
|
||||
In Vitro Model | B acute lymphoblastic leukemia | Reh cells | CVCL_1650 | ||
Experiment 11 Reporting the Activity Date of This ADC | [23] | ||||
Efficacy Data | Half Maximal Effective Concentration (EC50) |
162 nM
|
Low CD20 expression (CD20+) | ||
Method Description |
Cytotoxicity was determined using the MTS dye reduction assay.
|
||||
In Vitro Model | B acute lymphoblastic leukemia | Reh cells | CVCL_1650 | ||
Experiment 12 Reporting the Activity Date of This ADC | [23] | ||||
Efficacy Data | Half Maximal Effective Concentration (EC50) |
246.60 nM
|
High CD20 expression (CD20+++) | ||
Method Description |
Cytotoxicity was determined using the MTS dye reduction assay.
|
||||
In Vitro Model | EBV-related Burkitt lymphoma | Raji cells | CVCL_0511 |
References
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