Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0MBVTC
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| ADC Name |
Tras-Exa
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| Synonyms |
Trastuzumab + Val-Cit-Exatecan dendrimer
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| Organization |
Tel Aviv University.; Inter-Lab, a subsidiary of Merck KGaA.
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| Drug Status |
Investigative
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| Drug-to-Antibody Ratio |
4.3
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| Structure |
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| Antibody Name |
Trastuzumab
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Antibody Info | ||||
| Antigen Name |
Receptor tyrosine-protein kinase erbB-2 (ERBB2)
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Antigen Info | ||||
| Payload Name |
Exatecan
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Payload Info | ||||
| Therapeutic Target |
DNA topoisomerase 1 (TOP1)
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Target Info | ||||
| Linker Name |
AB2 self-immolative dendritic scaffold
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Linker Info | ||||
| Conjugate Type |
Random conjugation through reduced inter-chain cysteines.
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ADC-specific functional property(2027 Update)
Circulating Stability
| Incubation Time | 96h | Release | 0.4% | Reference |
[1]
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| Incubation Medium | Mouse serum | ||||
| Description |
First, we assessed the linker-drug stability of our trastuzumab-based ADCs in serum. To this end, Tras-Exa (DAR4), Tras-Bel (DAR4) and T-DXd (DAR8) were monitored overtime for their payload release in mouse and human sera (Table 2, Fig. S28) by the detection of free exatecan, belotecan and DXd via LC-MS/MS. Following 96 h incubation of the ADCs in sera, minimal amounts of the conjugated payload were released from both Tras-Exa and Tras-Bel ADCs in mouse (0.4% and 0.2%, respectively) and human (0.3% and 0.2%, respectively) sera.
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| Incubation Time | 96h | Release | 0.3% | Reference |
[1]
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| Incubation Medium | Human serum | ||||
| Description |
First, we assessed the linker-drug stability of our trastuzumab-based ADCs in serum. To this end, Tras-Exa (DAR4), Tras-Bel (DAR4) and T-DXd (DAR8) were monitored overtime for their payload release in mouse and human sera (Table 2, Fig. S28) by the detection of free exatecan, belotecan and DXd via LC-MS/MS. Following 96 h incubation of the ADCs in sera, minimal amounts of the conjugated payload were released from both Tras-Exa and Tras-Bel ADCs in mouse (0.4% and 0.2%, respectively) and human (0.3% and 0.2%, respectively) sera.
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General Information of The Activity Data Related to This ADC
Revealed Based on the Cell Line Data
Full List of Activity Data of This Antibody-drug Conjugate
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) | 0.6 nM | High HER2 expression (HER2 +++) | ||
| Method Description |
HCC-1954, JIMT-1 and MDA-MB-468 cells were plated in 24-well culture plates (5000, 5000 and 10,000 cells/well, respectively) and incubated for 24 h. Cells were then exposed to serial dilutions of trastuzumab, free exatecan, or Tras-Exa (DAR4) ADC. Cell viability was evaluated following 6 days of incubation using MTT (3 ug/mL, Sigma). MTT absorbance was measured at 570 nm using SpectraMax M5e multi-detection reader.
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| In Vitro Model | Breast ductal carcinoma | HCC-1954 cells | CVCL_1259 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) | 40 nM | Positive HER2 expression (HER2+++/++) | ||
| Method Description |
HCC-1954, JIMT-1 and MDA-MB-468 cells were plated in 24-well culture plates (5000, 5000 and 10,000 cells/well, respectively) and incubated for 24 h. Cells were then exposed to serial dilutions of trastuzumab, free exatecan, or Tras-Exa (DAR4) ADC. Cell viability was evaluated following 6 days of incubation using MTT (3 ug/mL, Sigma). MTT absorbance was measured at 570 nm using SpectraMax M5e multi-detection reader.
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| In Vitro Model | Breast ductal carcinoma | JIMT-1 cells | CVCL_2077 | ||
| Experiment 3 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) | 50 nM | Low HER2 expression (HER2+) | ||
| Method Description |
HCC-1954, JIMT-1 and MDA-MB-468 cells were plated in 24-well culture plates (5000, 5000 and 10,000 cells/well, respectively) and incubated for 24 h. Cells were then exposed to serial dilutions of trastuzumab, free exatecan, or Tras-Exa (DAR4) ADC. Cell viability was evaluated following 6 days of incubation using MTT (3 ug/mL, Sigma). MTT absorbance was measured at 570 nm using SpectraMax M5e multi-detection reader.
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| In Vitro Model | Breast adenocarcinoma | MDA-MB-468 cells | CVCL_0419 | ||
References