Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0HZNEP
ADC Name
Tmab-SPP-DM1
Synonyms
Tmab SPP DM1
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Drug Status
Investigative
Indication
In total 3 Indication(s)
Breast cancer [ICD11:2C60-2C65]
Investigative
Lung cancer [ICD11:2C25]
Investigative
Ovarian cancer [ICD11:2C73]
Investigative
Drug-to-Antibody Ratio
3-3.6
Structure
Antibody Name
Trastuzumab
  Antibody Info 
Antigen Name
Receptor tyrosine-protein kinase erbB-2 (ERBB2)
  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 conjugating with the free amino group on the antibody.
Combination Type
Mertansine
General Information of The Activity Data Related to This ADC
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Tumor Growth Inhibition value (TGI) 
≈ 77.6
%
MMTV-HER2 cells
Breast cancer
Revealed Based on the Cell Line Data
Click To Hide/Show 4 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Half Maximal Inhibitory Concentration (IC50) 
0.22
nM
SK-BR-3 cells
Breast adenocarcinoma
Half Maximal Inhibitory Concentration (IC50) 
4.26
nM
BT-474 cells
Invasive breast carcinoma
Half Maximal Inhibitory Concentration (IC50) 
41.37
nM
MDA-MB-468 cells
Breast adenocarcinoma
Half Maximal Inhibitory Concentration (IC50) 
> 100
nM
MCF-7 cells
Invasive breast carcinoma
Full List of Activity Data of This Antibody-drug Conjugate
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 [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 77.60% (Day 10) 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 [1]
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.

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In Vitro Model Breast adenocarcinoma SK-BR-3 cells CVCL_0033
Experiment 2 Reporting the Activity Date of This ADC [1]
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.

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In Vitro Model Invasive breast carcinoma BT-474 cells CVCL_0179
Experiment 3 Reporting the Activity Date of This ADC [1]
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.

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In Vitro Model Breast adenocarcinoma MDA-MB-468 cells CVCL_0419
Experiment 4 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 100.00 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.

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In Vitro Model Invasive breast carcinoma MCF-7 cells CVCL_0031
References
Ref 1 Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate. Cancer Res. 2008 Nov 15;68(22):9280-90.

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