Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0GSAHB
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| ADC Name |
W3195-1.53.1-p1-ulgG11-MMAE
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| Synonyms |
W3195-1.53.1-p1-ulgG11-MMAE
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| Organization |
WUXI BIOLOGICS IRELAND LIMITED
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| Drug Status |
Investigative
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| Structure |
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| Antibody Name |
W3195-1.53.1-p1-ulgG11
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Antibody Info | ||||
| Antigen Name |
Cadherin-3 (CDH3)
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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 |
Mc-Val-Cit-PABC
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Linker Info | ||||
| Conjugate Type |
Random conjugation through reduced inter-chain cysteines.
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| Combination Type |
Vedotin
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ADC-specific functional property(2027 Update)
Binding Affinity
| Dissocation Constant (Kd) | Binding Target | Description | Reference |
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| Undisclosed | Undisclosed |
The FACS binding activity of W3195-1.53.1-p1-ulgG11-MMAE to HCT-116 cells with EC50 0.17 nM and Max MFI of 6164.The FACS binding activity of W3195-1.53.1-p1-ulgG11-MMAE to NCI-H1650 cells with EC50 0.075 nM and Max MFI of 3005.
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[1]
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Bystander Killing Effect
| Bystander Killing Effect | Description | Reference |
|---|---|---|
| no | Undisclosed |
[1]
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General Information of The Activity Data Related to This ADC
Discovered Using Cell Line-derived Xenograft Model
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) |
85.15%
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| Method Description |
Cell line-derived xenograft models were established in SCID-17B female mice, by subcutaneous injection of 1x107 (HCC-70) tumor cells, and treatmen with 1mg/kg ADC (single dosee) after tumor volume about 230mm3. Determined tumor volume after the experiment, measured at day 34.
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| In Vivo Model | HCC70 breast tumor model | ||||
| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) |
38.69%
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| Method Description |
Cell line-derived xenograft models were established in SCID-17B female mice, by subcutaneous injection of 5x106 (NCI-H1650) tumor cells, and treatmen with 2.5mg/kg ADC (single dosee) after tumor volume about 137mm3. Determined tumor volume after the experiment, measured at day 31.
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| In Vivo Model | NCI-H1650 breast tumor model | ||||
| Experiment 3 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) |
62.06%
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| Method Description |
Cell line-derived xenograft models were established in SCID-17B female mice, by subcutaneous injection of 1x107 (HCC-70) tumor cells, and treatmen with 0.5mg/kg ADC (single dosee) after tumor volume about 242mm3. Determined tumor volume after the experiment, measured at day 36.
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| In Vivo Model | HCC70 breast tumor model | ||||
| Experiment 4 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) |
107.99%
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| Method Description |
Cell line-derived xenograft models were established in SCID-17B female mice, by subcutaneous injection of 5x106 (NCI-H1650) tumor cells, and treatmen with 5mg/kg ADC (single dosee) after tumor volume about 137mm3. Determined tumor volume after the experiment, measured at day 31.
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| In Vivo Model | NCI-H1650 breast tumor model | ||||
| Experiment 5 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) |
107.99%
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| Method Description |
Cell line-derived xenograft models were established in SCID-17B female mice, by subcutaneous injection of 5x106 (NCI-H1650) tumor cells, and treatmen with 5mg/kg ADC (single dosee) after tumor volume about 137mm3. Determined tumor volume after the experiment, measured at day 31.
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| In Vivo Model | NCI-H1650 breast tumor model | ||||
| Experiment 6 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) |
122.67%
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| Method Description |
Cell line-derived xenograft models were established in SCID-17B female mice, by subcutaneous injection of 1x107 (HCC-70) tumor cells, and treatmen with 2.5mg/kg ADC (single dosee) after tumor volume about 242mm3. Determined tumor volume after the experiment, measured at day 36.
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| In Vivo Model | HCC70 breast tumor 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..011 nM
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| Method Description |
4000cells/well for HCC-1954 (50 uL) of cells from each cell line were seeded onto 96-well clear bottom black plates. The cells were cultured overnight at 37°C in a humidified 5% CO2 incubator before adding the ADC, The plates were returned to the incubator for 5 days . 50 uL of CellTiter Glo solution was added to each well and incubated atroom temperature with gentle shaking for 10 minutes.
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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) |
0.027 nM
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| Method Description |
2000 cells/well for NCI-H1650 (50 uL) of cells from each cell line were seeded onto 96-well clear bottom black plates. The cells were cultured overnight at 37°C in a humidified 5% CO2 incubator before adding the ADC, The plates were returned to the incubator for 5 days . 50 uL of CellTiter Glo solution was added to each well and incubated atroom temperature with gentle shaking for 10 minutes.
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| In Vitro Model | Lung adenocarcinoma | NCI-H1650 cells | CVCL_1483 | ||
| Experiment 3 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) |
0.065 nM
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| Method Description |
6000 cells/well for HCC-70 (50 uL) of cells from each cell line were seeded onto 96-well clear bottom black plates. The cells were cultured overnight at 37°C in a humidified 5% CO2 incubator before adding the ADC, The plates were returned to the incubator for 5 days . 50 uL of CellTiter Glo solution was added to each well and incubated atroom temperature with gentle shaking for 10 minutes.
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| In Vitro Model | Breast ductal carcinoma | HCC-70 cells | CVCL_1270 | ||
| Experiment 4 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) | > 10 nM | |||
| Method Description |
5000cells/well for HT-29 (50 uL) of cells from each cell line were seeded onto 96-well clear bottom black plates. The cells were cultured overnight at 37°C in a humidified 5% CO2 incubator before adding the ADC, The plates were returned to the incubator for 5 days . 50 uL of CellTiter Glo solution was added to each well and incubated atroom temperature with gentle shaking for 10 minutes.
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| In Vitro Model | Colon adenocarcinoma | HT-29 cells | CVCL_0320 | ||
| Experiment 5 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) | > 10 nM | |||
| Method Description |
800 cells/well for A549 (50 uL) of cells from each cell line were seeded onto 96-well clear bottom black plates. The cells were cultured overnight at 37°C in a humidified 5% CO2 incubator before adding the ADC, The plates were returned to the incubator for 5 days . 50 uL of CellTiter Glo solution was added to each well and incubated atroom temperature with gentle shaking for 10 minutes.
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| In Vitro Model | Lung adenocarcinoma | A549 cells | CVCL_0023 | ||
| Experiment 6 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) | > 10 nM | |||
| Method Description |
5000 cells/well for MDA-MB-453 (50 uL) of cells from each cell line were seeded onto 96-well clear bottom black plates. The cells were cultured overnight at 37°C in a humidified 5% CO2 incubator before adding the ADC, The plates were returned to the incubator for 5 days . 50 uL of CellTiter Glo solution was added to each well and incubated atroom temperature with gentle shaking for 10 minutes.
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| In Vitro Model | Breast adenocarcinoma | MDA-MB-453 cells | CVCL_0418 | ||
| Experiment 7 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) |
0.023 nM
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| Method Description |
For HCC-1954 cells,cells were washed with 100uL,1% BSA1xPBS resuspended in PE conjugated Goatanti-human IgG Fc 1:150 dilutedin 1% BSA1xPBS for 1 hour at 4°C in thedark. Cells were then washed one time as described aboveand resuspended in 1% BSA/1xPBS for 2 hours at 37°C. Supernatants were discarded and 100 uL/wellquench buffer (0.1 M glycine, 0.15 M NaCl, adjust pH to2.5) were added and incubated at 4°C. for 5 min. Cells werethen washed one time as described above and resuspended in Hoechst 33342 1:5000 diluted in DPBS for 15 min at room tem-perature.Afer washed with DPBS one time as described above, cells were resuspended in 4%%PFA and stored at 4°C.
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| In Vitro Model | Breast ductal carcinoma | HCC-1954 cells | CVCL_1259 | ||
| Experiment 8 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) |
0.18 nM
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| Method Description |
The thawed antibodies were serially diluted and added to 1x103 well (HCT-116) and incubated for 1 hourat 4°C.ADC were added to the cells and incubated at 4°C for30 minutes. Cells were washed twice in the same bufer andthe mean fluorescence (MFl) of stained cells was measuredusing a FACS Canto I cytometer (BD Biosciences)andanalyzed by FlowJo. Wells containing no antibody or sec-ondary antibody only were used to establish background fluorescence. Four-parameter non-linear regression analysiswas used to obtain EC50 values for cell binding usingGraphPad Prism6 software at Day14.
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| Experiment 9 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) |
0.22 nM
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| Method Description |
For NCI-H1650 cells,cells were washed with 100uL,1% BSA/1xPBS resuspended in Alexa647 conjugatedGoat anti-human IgG Fc 1:500 diluted in 1% BSA/1xPBS for 1 hour at 4°C. inthe dark.Cells were then washed one time as describedabove and resuspended in 1% BSA/1xPBS for 2hours at 37°C. Supernatants were discarded and cells wereresuspended in Hoechst 33342 1:5000diluted in DPBS for 15 min atroom temperature.After washed with DPBS one time as described above,100 uL/well quench buffer (0.1 M glycine, 0.15 M NaCl, adjust pH to2.5)were added and incubated at 4°C.for 5 min. Afterwashing for once with 1% BSA/1xPBS, cellswere resuspended in 4% PFA and stored at 4°C
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| In Vitro Model | Lung adenocarcinoma | NCI-H1650 cells | CVCL_1483 | ||