Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0TUCHR
ADC Name
Mirvetuximab-SPP-DM1
Drug Status
Investigative
Indication
In total 4 Indication(s)
Cervical cancer [ICD11:2C77]
Investigative
Gestational choriocarcinoma [ICD11:2C75]
Investigative
Lung cancer [ICD11:2C25]
Investigative
Ovarian cancer [ICD11:2C73]
Investigative
Drug-to-Antibody Ratio
3.6-4.3
Structure
Antibody Name
Mirvetuximab
  Antibody Info 
Antigen Name
Folate receptor alpha (FOLR1)
  Antigen Info 
Payload Name
Mertansine DM1
  Payload Info 
Therapeutic Target
Microtubule (MT)
  Target Info 
Linker Name
N-succinimidyl 4-(2-pyridyldithio) pentanoate (SPP)
  Linker Info 
Conjugate Type
Random conjugation through nucleophilic lysines.
Combination Type
Mertansine
General Information of The Activity Data Related to This ADC
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Tumor Growth Inhibition value (TGI) 
32.17
%
KB cells
Human papillomavirus-related endocervical adenocarcinoma
Tumor Growth Inhibition value (TGI) 
50
%
IGROV-1 cells
Ovarian endometrioid adenocarcinoma
Revealed Based on the Cell Line Data
Click To Hide/Show 3 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Half Maximal Inhibitory Concentration (IC50) 
0.11±0.04
nM
KB cells
Human papillomavirus-related endocervical adenocarcinoma
Half Maximal Inhibitory Concentration (IC50) 
0.13±0.08
nM
JEG-3 cells
Gestational choriocarcinoma
Half Maximal Inhibitory Concentration (IC50) 
0.14±0.05
nM
IGROV-1 cells
Ovarian endometrioid adenocarcinoma
Full List of Activity Data of This Antibody-drug Conjugate
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 [1]
Efficacy Data Tumor Growth Inhibition value (TGI) 32.17% (Day 30) 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 2.5±0.2 mg/kg, equivalent to 51±3 ug 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 [1]
Efficacy Data Tumor Growth Inhibition value (TGI) 50.00% (Day 32) 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 2.5±0.2 mg/kg, equivalent to 51±3 ug 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 [1]
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 [1]
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 [1]
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
References
Ref 1 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.

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