Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0BHKME
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| ADC Name |
WO2023047090A1-MMAE ADC
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| Synonyms |
MMAE ADC
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| Organization |
SPIREA LIMITED
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| Drug Status |
Investigative
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| Drug-to-Antibody Ratio |
17.1
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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 |
Monomethyl auristatin E
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Payload Info | ||||
| Therapeutic Target |
Microtubule (MT)
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Target Info | ||||
| Linker Name |
Undisclosed
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| Conjugate Type |
Random conjugation through reduced inter-chain cysteines.
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| Combination Type |
Hydroxylamine-vc-PAB-MMAE
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ADC-specific functional property(2027 Update)
Circulating Stability
| Incubation Time | 96hours | Release | 16% | Reference |
[1]
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| Incubation Medium | mouse plasma | ||||
| Description |
ADCs were spiked into mouse serum and incubated at 37 °C over a 96-hour period. To evaluatethe changes in DAR profile throughout serum incubation, ADCs were analysed by HIC-UV (280nm) after being isolated from serum using affinity capture.
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Bystander Killing Effect
| Bystander Killing Effect | Description | Reference |
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| no | Undisclosed |
[1]
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General Information of The Activity Data Related to This ADC
Discovered Using Cell Line-derived Xenograft Model
| Standard Type | Value | Units | Cell Line | Disease Model |
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| Tumor Growth lnhibition value (TGl) |
80.32
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%
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Undisclosed | Undisclosed |
| Tumor Growth lnhibition value (TGl) |
107.47
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%
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Undisclosed | Undisclosed |
Revealed Based on the Cell Line Data
Full List of Activity Data of This Antibody-drug Conjugate
Discovered Using Cell Line-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth lnhibition value (TGl) | 80.32% | Positive her2 expression (her2+++/++) | ||
| Method Description |
Cell line-derived xenograft models were established in in female BALB/c Nude mice, by subcutaneous injection of 1x106 (NCI-N87) tumor cells, and treatmen with 1.33mg/kg ADC (single dosee) after tumor volume about 198mm3. Determined tumor volume after the experiment, measured at day 36.
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| In Vivo Model | NCI-N87 xenograft model | ||||
| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth lnhibition value (TGl) | 107.47% | Positive her2 expression (her2+++/++) | ||
| Method Description |
Cell line-derived xenograft models were established in in female BALB/c Nude mice, by subcutaneous injection of 1x106 (NCI-N87) tumor cells, and treatmen with 4mg/kg ADC (single dosee) after tumor volume about 198mm3. Determined tumor volume after the experiment, measured at day 36.
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| In Vivo Model | NCI-N87 xenograft model | ||||
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) | 0.008 nM | High HER2 expression (HER2 +++) | ||
| Method Description |
5000cells/well for SK-BR-3 (100 uL) of cells were seeded onto 96-well plates and incubated for 24 hours before adding the ADC. After 24 hours, growth medium was replaced with ADC in growth medium. After 96 hours, viability was detected using the CellTiter-Glo® luminescence assay. Assay plates were equilibrated at room temperature for 20 minutes before addition of 100ul CellTiter-Glo® reagent per well. The plates were then mixed for 3minutes at 300 rpm to assist cell lysis and incubated for a further 20 minutes at room temperatureto stabilise the luminescence signal. Luminescence was recorded using a SpectraMax i3x platereader with a default integration time of 0.5 s/well.
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| In Vitro Model | Breast ductal carcinoma | JIMT-1 cells | CVCL_2077 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) | 0.228 nM | Low HER2 expression (HER2+) | ||
| Method Description |
2000cells/well for JIMT-1 (100 uL) of cells were seeded onto 96-well plates and incubated for 24 hours before adding the ADC. After 24 hours, growth medium was replaced with ADC in growth medium. After 96 hours, viability was detected using the CellTiter-Glo® luminescence assay. Assay plates were equilibrated at room temperature for 20 minutes before addition of 100ul CellTiter-Glo® reagent per well. The plates were then mixed for 3minutes at 300 rpm to assist cell lysis and incubated for a further 20 minutes at room temperatureto stabilise the luminescence signal. Luminescence was recorded using a SpectraMax i3x platereader with a default integration time of 0.5 s/well.
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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) | > 100 nM | Negative HER2 expression (HER2-) | ||
| Method Description |
2500cells/well for NCI-H520 (100 uL) of cells were seeded onto 96-well plates and incubated for 24 hours before adding the ADC. After 24 hours, growth medium was replaced with ADC in growth medium. After 96 hours, viability was detected using the CellTiter-Glo® luminescence assay. Assay plates were equilibrated at room temperature for 20 minutes before addition of 100ul CellTiter-Glo® reagent per well. The plates were then mixed for 3minutes at 300 rpm to assist cell lysis and incubated for a further 20 minutes at room temperatureto stabilise the luminescence signal. Luminescence was recorded using a SpectraMax i3x platereader with a default integration time of 0.5 s/well.
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| In Vitro Model | Lung squamous cell carcinoma | NCI-H520 cells | CVCL_1566 | ||