Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0XHBXX
ADC Name
WO2017059289A1 ADC-107
Synonyms
Thio Hu Anti-CD22 10F4v3 LC K149C-52
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Organization
Genentech, Inc.
Drug Status
Investigative
Indication
In total 1 Indication(s)
Diffuse large B-cell lymphoma [ICD11:2A81]
Investigative
Drug-to-Antibody Ratio
1.95
Antibody Name
Thio hu Anti-CD22 10F4v3 LC K149C
  Antibody Info 
Antigen Name
B-cell receptor CD22 (CD22)
  Antigen Info 
Payload Name
Undisclosed
Linker Name
WO2017059289A1_ADC-107 linker
General Information of The Activity Data Related to This ADC
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 5 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Tumor Growth Inhibition value (TGI) 
≈ 43.13
%
KPL-4 cells
Breast inflammatory carcinoma
Tumor Growth Inhibition value (TGI) 
≈ 66.14
%
WSU-DLCL2 cells
Diffuse large B-cell lymphoma
Tumor Growth Inhibition value (TGI) 
≈ 89.73
%
WSU-DLCL2 cells
Diffuse large B-cell lymphoma
Tumor Growth Inhibition value (TGI) 
≈ 94.54
%
WSU-DLCL2 cells
Diffuse large B-cell lymphoma
Tumor Growth Inhibition value (TGI) 
≈ 98.06
%
WSU-DLCL2 cells
Diffuse large B-cell lymphoma
Obtained from the Model Organism Data
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) 
≈ 23.58
%
Breast cancer model MMTV-HER2 Fo5
Revealed Based on the Cell Line Data
Click To Hide/Show 8 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Half Maximal Inhibitory Concentration (IC50) 
1.56
nM
WSU-DLCL2 cells
Diffuse large B-cell lymphoma
Half Maximal Inhibitory Concentration (IC50) 
1.7
nM
BJAB cells
Burkitt lymphoma
Half Maximal Inhibitory Concentration (IC50) 
8.7
nM
Jurkat cells
T acute lymphoblastic leukemia
Half Maximal Inhibitory Concentration (IC50) 
44.5
ng/mL
SK-BR-3 cells
Breast adenocarcinoma
Half Maximal Inhibitory Concentration (IC50) 
57.4
ng/mL
KPL-4 cells
Breast inflammatory carcinoma
Half Maximal Inhibitory Concentration (IC50) 
234.11
ng/mL
WSU-DLCL2 cells
Diffuse large B-cell lymphoma
Half Maximal Inhibitory Concentration (IC50) 
254.2
ng/mL
BJAB cells
Burkitt lymphoma
Half Maximal Inhibitory Concentration (IC50) 
1303.63
ng/mL
Jurkat cells
T acute lymphoblastic leukemia
Full List of Activity Data of This Antibody-drug Conjugate
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 5 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 43.13% (Day 24) Positive HER2 expression (HER2+++/++)
Method Description
Inoculate 150 mice with KPL-4 cells at 3 million cells/mouse suspended in HBSS/matrigel, in the thoracic mammary fat pad at a volume of 0.2 ml. When tumors have reached a mean tumor volume of 100-250 mm3, they will be grouped out into 10 groups of 8-10 mice each. A single treatment will be administered intravenously (1 mg/kg) via the tail vein on Day 0.

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In Vivo Model KPL-4 CDX model
In Vitro Model Breast inflammatory carcinoma KPL-4 cells CVCL_5310
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 66.14% (Day 12) Positive CD22 expression (CD22+++/++)
Method Description
Inoculate 150 mice with WSU-DLCL2 cells at 3 million cells/mouse suspended in HBSS/matrigel, in the thoracic mammary fat pad at a volume of 0.2 ml. When tumors have reached a mean tumor volume of 100-250 mm3, they will be grouped out into 10 groups of 8-10 mice each. A single treatment will be administered intravenously (0.5 mg/kg) via the tail vein on Day 0.

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In Vivo Model WSU-DLCL2 CDX model
In Vitro Model Diffuse large B-cell lymphoma WSU-DLCL2 cells CVCL_1902
Experiment 3 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 89.73% (Day 12) Positive CD22 expression (CD22+++/++)
Method Description
Inoculate 150 mice with WSU-DLCL2 cells at 3 million cells/mouse suspended in HBSS/matrigel, in the thoracic mammary fat pad at a volume of 0.2 ml. When tumors have reached a mean tumor volume of 100-250 mm3, they will be grouped out into 10 groups of 8-10 mice each. A single treatment will be administered intravenously (2 mg/kg) via the tail vein on Day 0.

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In Vivo Model WSU-DLCL2 CDX model
In Vitro Model Diffuse large B-cell lymphoma WSU-DLCL2 cells CVCL_1902
Experiment 4 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 94.54% (Day 12) Positive CD22 expression (CD22+++/++)
Method Description
Inoculate 150 mice with WSU-DLCL2 cells at 3 million cells/mouse suspended in HBSS/matrigel, in the thoracic mammary fat pad at a volume of 0.2 ml. When tumors have reached a mean tumor volume of 100-250 mm3, they will be grouped out into 10 groups of 8-10 mice each. A single treatment will be administered intravenously (5 mg/kg) via the tail vein on Day 0.

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In Vivo Model WSU-DLCL2 CDX model
In Vitro Model Diffuse large B-cell lymphoma WSU-DLCL2 cells CVCL_1902
Experiment 5 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 98.06% (Day 12) Positive CD22 expression (CD22+++/++)
Method Description
Inoculate 150 mice with WSU-DLCL2 cells at 3 million cells/mouse suspended in HBSS/matrigel, in the thoracic mammary fat pad at a volume of 0.2 ml. When tumors have reached a mean tumor volume of 100-250 mm3, they will be grouped out into 10 groups of 8-10 mice each. A single treatment will be administered intravenously (10 mg/kg) via the tail vein on Day 0.

   Click to Show/Hide
In Vivo Model WSU-DLCL2 CDX model
In Vitro Model Diffuse large B-cell lymphoma WSU-DLCL2 cells CVCL_1902
Obtained from the Model Organism Data
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) ≈ 23.58% (Day 7) Positive HER2 expression (HER2+++/++)
Method Description
Before being used for an in vivo efficacy study, the MMTV-HER2 Fo5 transgenic mammary tumor was surgically transplanted into the mammary fat pad of nu/nu mice in fragments that measured approximately 2x2 mm. MMTV-HER2 Fo5 mammary allograft tumors inoculated into CRL nu/nu mice aftersingle,then iv 2 mg/kg ADC dosing on day 0.
In Vivo Model Breast cancer model MMTV-HER2 Fo5
Revealed Based on the Cell Line Data
Click To Hide/Show 8 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 1.56 nM Positive CD22 expression (CD22+++/++)
Method Description
Cell-based in vitro assays are used to measure viability (proliferation), cytotoxicity,and induction of apoptosis of the ADC of the invention. Culturing the cells for a period from about 6 hours to about 5 days and measuring cell viability.
In Vitro Model Diffuse large B-cell lymphoma WSU-DLCL2 cells CVCL_1902
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 1.70 nM Positive CD22 expression (CD22+++/++)
Method Description
Cell-based in vitro assays are used to measure viability (proliferation), cytotoxicity,and induction of apoptosis of the ADC of the invention. Culturing the cells for a period from about 6 hours to about 5 days and measuring cell viability.
In Vitro Model Burkitt lymphoma BJAB cells CVCL_5711
Experiment 3 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 8.70 nM Positive CD22 expression (CD22+++/++)
Method Description
Cell-based in vitro assays are used to measure viability (proliferation), cytotoxicity,and induction of apoptosis of the ADC of the invention. Culturing the cells for a period from about 6 hours to about 5 days and measuring cell viability.
In Vitro Model T acute lymphoblastic leukemia Jurkat cells CVCL_0065
Experiment 4 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 44.50 ng/mL High HER2 expression (HER2 +++)
Method Description
Cell-based in vitro assays are used to measure viability (proliferation), cytotoxicity,and induction of apoptosis of the ADC of the invention. Culturing the cells for a period from about 6 hours to about 5 days and measuring cell viability.
In Vitro Model Breast adenocarcinoma SK-BR-3 cells CVCL_0033
Experiment 5 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 57.40 ng/mL High HER2 expression (HER2+++)
Method Description
Cell-based in vitro assays are used to measure viability (proliferation), cytotoxicity,and induction of apoptosis of the ADC of the invention. Culturing the cells for a period from about 6 hours to about 5 days and measuring cell viability.
In Vitro Model Breast inflammatory carcinoma KPL-4 cells CVCL_5310
Experiment 6 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 234.11 ng/mL Positive CD22 expression (CD22+++/++)
Method Description
Cell-based in vitro assays are used to measure viability (proliferation), cytotoxicity,and induction of apoptosis of the ADC of the invention. Culturing the cells for a period from about 6 hours to about 5 days and measuring cell viability.
In Vitro Model Diffuse large B-cell lymphoma WSU-DLCL2 cells CVCL_1902
Experiment 7 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 254.20 ng/mL Positive CD22 expression (CD22+++/++)
Method Description
Cell-based in vitro assays are used to measure viability (proliferation), cytotoxicity,and induction of apoptosis of the ADC of the invention. Culturing the cells for a period from about 6 hours to about 5 days and measuring cell viability.
In Vitro Model Burkitt lymphoma BJAB cells CVCL_5711
Experiment 8 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 1303.63 ng/mL Positive CD22 expression (CD22+++/++)
Method Description
Cell-based in vitro assays are used to measure viability (proliferation), cytotoxicity,and induction of apoptosis of the ADC of the invention. Culturing the cells for a period from about 6 hours to about 5 days and measuring cell viability.
In Vitro Model T acute lymphoblastic leukemia Jurkat cells CVCL_0065
References
Ref 1 Pyrrolobenzodiazepine antibody drug conjugates and methods of use; 2017-04-06.

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