General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0JSUAX
ADC Name
huNeg8.8-vc6780
Synonyms
huNeg8.8 vc6780
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Organization
Pfizer Inc.
Drug Status
Investigative
Indication
In total 4 Indication(s)
Breast cancer [ICD11:2C60-2C65]
Investigative
Non small cell lung cancer [ICD11:2C25]
Investigative
Osteosarcoma [ICD11:2B51]
Investigative
Ovarian cancer [ICD11:2C73]
Investigative
Drug-to-Antibody Ratio
4.1
Antibody Name
Anti-NOTCH3 mAb huNeg8.8
 Antibody Info 
Antigen Name
Neurogenic locus notch homolog protein 3 (NOTCH3)
 Antigen Info 
Payload Name
Undisclosed
Linker Name
huNeg8.8-vc6780 linker
General Information of The Activity Data Related to This ADC
Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Standard Type Value Units Animal Model (No. of PDX)
Tumor Growth Inhibition value (TGI) 
≈ 15.5
%
Non small cell lung cancer PDX model (PDX: 37622A1)
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 8 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Tumor Growth Inhibition value (TGI) 
≈ 0
%
CVCL_0419
Breast adenocarcinoma
Tumor Growth Inhibition value (TGI) 
≈ 1.4
%
CVCL_0419
Breast adenocarcinoma
Tumor Growth Inhibition value (TGI) 
≈ 1.8
%
CVCL_5132
Lung non-small cell carcinoma
Tumor Growth Inhibition value (TGI) 
≈ 12.9
%
CVCL_1603
Gastric tubular adenocarcinoma
Tumor Growth Inhibition value (TGI) 
≈ 15.8
%
CVCL_5132
Lung non-small cell carcinoma
Tumor Growth Inhibition value (TGI) 
≈ 29
%
CVCL_5132
Lung non-small cell carcinoma
Tumor Growth Inhibition value (TGI) 
≈ 38.2
%
CVCL_0419
Breast adenocarcinoma
Tumor Growth Inhibition value (TGI) 
≈ 50.5
%
CVCL_1603
Gastric tubular adenocarcinoma
Revealed Based on the Cell Line Data
Click To Hide/Show 2 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Half Maximal Inhibitory Concentration (IC50) 
0
ug/mL
CVCL_0419
Breast adenocarcinoma
Half Maximal Inhibitory Concentration (IC50) 
0
ug/mL
CVCL_0465
Ovarian serous adenocarcinoma
Full List of Activity Data of This Antibody-drug Conjugate
Discovered Using Patient-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) ≈ 15.50% (Day 60) Positive NOTCH3 expression (NOTCH3+++/++)
Method Description
Cells were subcutaneously inoculated at a dose of 1,000,000 cells to the right flank region of each female nude mouse (Day 0). On the day 7 of grouping, the antibody-drug conjugate was intravenously administered at doses of 10 mg/kg, Q4d*4 to thetail of each mouse.
In Vivo Model Non small cell lung cancer PDX model (PDX: 37622A1)
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 8 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 0.00% (Day 19) Positive NOTCH3 expression (NOTCH3+++/++)
Method Description
Cells were subcutaneously inoculated at a dose of 1,000,000 cells to the right flank region of each female nude mouse (Day 0). On the day 7 of grouping, the antibody-drug conjugate was intravenously administered at doses of 1 mg/kg, Q4d*4 to thetail of each mouse.
In Vivo Model MDA-MB-468 CDX model
In Vitro Model Breast adenocarcinoma MDA-MB-468 cells CVCL_0419
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 1.40% (Day 19) Positive NOTCH3 expression (NOTCH3+++/++)
Method Description
Cells were subcutaneously inoculated at a dose of 1,000,000 cells to the right flank region of each female nude mouse (Day 0). On the day 7 of grouping, the antibody-drug conjugate was intravenously administered at doses of 3 mg/kg, Q4d*4 to thetail of each mouse.
In Vivo Model MDA-MB-468 CDX model
In Vitro Model Breast adenocarcinoma MDA-MB-468 cells CVCL_0419
Experiment 3 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 1.80% (Day 10) Positive NOTCH3 expression (NOTCH3+++/++)
Method Description
Cells were subcutaneously inoculated at a dose of 1,000,000 cells to the right flank region of each female nude mouse (Day 0). On the day 7 of grouping, the antibody-drug conjugate was intravenously administered at doses of 3 mg/kg, Q4d*4 to thetail of each mouse.
In Vivo Model HCC2429 CDX model
In Vitro Model Lung non-small cell carcinoma HCC2429 cells CVCL_5132
Experiment 4 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 12.90% (Day 33) Positive NOTCH3 expression (NOTCH3+++/++)
Method Description
Cells were subcutaneously inoculated at a dose of 1,000,000 cells to the right flank region of each female nude mouse (Day 0). On the day 7 of grouping, the antibody-drug conjugate was intravenously administered at doses of 3 mg/kg, Q4d*4 to thetail of each mouse.
In Vivo Model NCI-N87 CDX model
In Vitro Model Gastric tubular adenocarcinoma NCI-N87 cells CVCL_1603
Experiment 5 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 15.80% (Day 10) Positive NOTCH3 expression (NOTCH3+++/++)
Method Description
Cells were subcutaneously inoculated at a dose of 1,000,000 cells to the right flank region of each female nude mouse (Day 0). On the day 7 of grouping, the antibody-drug conjugate was intravenously administered at doses of 1 mg/kg, Q4d*4 to thetail of each mouse.
In Vivo Model HCC2429 CDX model
In Vitro Model Lung non-small cell carcinoma HCC2429 cells CVCL_5132
Experiment 6 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 29.00% (Day 10) Positive NOTCH3 expression (NOTCH3+++/++)
Method Description
Cells were subcutaneously inoculated at a dose of 1,000,000 cells to the right flank region of each female nude mouse (Day 0). On the day 7 of grouping, the antibody-drug conjugate was intravenously administered at doses of 10 mg/kg, Q4d*4 to thetail of each mouse.
In Vivo Model HCC2429 CDX model
In Vitro Model Lung non-small cell carcinoma HCC2429 cells CVCL_5132
Experiment 7 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 38.20% (Day 19) Positive NOTCH3 expression (NOTCH3+++/++)
Method Description
Cells were subcutaneously inoculated at a dose of 1,000,000 cells to the right flank region of each female nude mouse (Day 0). On the day 7 of grouping, the antibody-drug conjugate was intravenously administered at doses of 10 mg/kg, Q4d*4 to thetail of each mouse.
In Vivo Model MDA-MB-468 CDX model
In Vitro Model Breast adenocarcinoma MDA-MB-468 cells CVCL_0419
Experiment 8 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 50.50% (Day 33) Positive NOTCH3 expression (NOTCH3+++/++)
Method Description
Cells were subcutaneously inoculated at a dose of 1,000,000 cells to the right flank region of each female nude mouse (Day 0). On the day 7 of grouping, the antibody-drug conjugate was intravenously administered at doses of 10 mg/kg, Q4d*4 to thetail of each mouse.
In Vivo Model NCI-N87 CDX model
In Vitro Model Gastric tubular adenocarcinoma NCI-N87 cells CVCL_1603
Revealed Based on the Cell Line Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 6.55 ug/mL Positive NOTCH3 expression (NOTCH3+++/++)
Method Description
The MTS cell proliferation assay was performed as follows: CellTiter 96 Aqueous Non-Radioactive Cell proliferation Kit is used to determine the number of viable cells in cell proliferation assay. Tumor cells are plated at certain seeding densities in sterile 384-well black clear bottom Matrix plates at 40 uL per well and incubated overnight at 37°C in 5% CO2 before assaying.

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In Vitro Model Breast adenocarcinoma MDA-MB-468 cells CVCL_0419
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 9.24 ug/mL Positive NOTCH3 expression (NOTCH3+++/++)
Method Description
The MTS cell proliferation assay was performed as follows: CellTiter 96 Aqueous Non-Radioactive Cell proliferation Kit is used to determine the number of viable cells in cell proliferation assay. Tumor cells are plated at certain seeding densities in sterile 384-well black clear bottom Matrix plates at 40 uL per well and incubated overnight at 37°C in 5% CO2 before assaying.

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In Vitro Model Ovarian serous adenocarcinoma OVCAR-3 cells CVCL_0465
References
Ref 1 Anti-notch3 antibodies and antibody-drug conjugates.

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