Antibody Information

General Information of This Antibody

Antibody ID	ANI0TAEHM
Antibody Name	Mipasetamab
Organization	ADC Therapeutics SA
Indication	Solid tumors
Synonyms	1H12; 1H12-GaINAcN3; 1H12-GALNACN3; 1H12-HAKB; BGB-601 Click to Show/Hide
Antibody Type	Monoclonal antibody (mAb)
Antibody Subtype	Humanized IgG1-kappa
Antigen Name	Tyrosine-protein kinase receptor UFO (AXL)	Antigen Info
ChEMBI ID	CHEMBL5095447
Click to Show/Hide the Sequence Information of This Antibody
Heavy Chain Sequence	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMSWVRQAPGKGLEWVATISSGGSYTYY PDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARHPIYYTYDDTMDYWGQGTTVTV SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ SSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS R EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD KS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPG Click to Show/Hide
Heavy Chain Varible Domain	QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMSWVRQAPGKGLEWVATISSGGSYTYY PDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARHPIYYTYDDTMDYWGQGTTVTV SS Click to Show/Hide
Heavy Chain Constant Domain 1	ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKV Click to Show/Hide
Heavy Chain Constant Domain 2	APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK PREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK Click to Show/Hide
Heavy Chain Constant Domain 3	GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG Click to Show/Hide
Heavy Chain Hinge Region	EPKSCDKTHTCPPCP Click to Show/Hide
Heavy Chain CDR 1	GFTFSSYG Click to Show/Hide
Heavy Chain CDR 2	ISSGGSYT Click to Show/Hide
Heavy Chain CDR 3	ARHPIYYTYDDTMDY Click to Show/Hide
Light Chain Sequence	EIVLTQSPGTLSLSPGERATLSCSASSSVSSGNFHWYQQKPGLAPRLLIYRTSNLASGIP ARFSGSGSGTDFTLTISSLEPEDFAVYYCQQWSGYPWTFGGGTKLEIKRTVAAPSVFIFP PSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTL TLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC Click to Show/Hide
Light Chain Varible Domain	EIVLTQSPGTLSLSPGERATLSCSASSSVSSGNFHWYQQKPGLAPRLLIYRTSNLASGIP ARFSGSGSGTDFTLTISSLEPEDFAVYYCQQWSGYPWTFGGGTKLEIK Click to Show/Hide
Light Chain Constant Domain	RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC Click to Show/Hide
Light Chain CDR 1	SSVSSGN Click to Show/Hide
Light Chain CDR 2	RTS Click to Show/Hide
Light Chain CDR 3	QQWSGYPWT Click to Show/Hide

Each Antibody-drug Conjugate Related to This Antibody

Full Information of The Activity Data of The ADC(s) Related to This Antibody

Mipasetamab uzoptirine [Phase 1]

ADC Info

Discovered Using Patient-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)	≈ 35.00% (Day 65)	Positive AXL expression (AXL+++/++)
Method Description	In vivo antitumor activity of ADCT-601 in BRCA1-mutated ovarian cancer PDX model. Single-dose (0.15 mg/kg,q.d.) ADCT-601 and isotype-control ADC (B12-PL1601) were administered intravenously (day 1) to treatment groups of 8 mice.
In Vivo Model	BRCA1-mutated ovarian cancer PDX model (PDX: CTG-0703)
Experiment 2 Reporting the Activity Date of This ADC				[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 57.40% (Day 21)	Positive AXL expression (AXL+++/++)
Method Description	The antitumor activity of ADCT-601 was tested in a range of human solid tumor xenograft models covering multiple indications. Single-dose (0.075 mg/kg,q.d.). ADCT-601 and isotype-control ADC (B12-PL1601) were administered intravenously (day 1) to treatment groups of 8 mice.
In Vivo Model	Pancreatic cancer PDX model (PDX: PAXF1657)
Experiment 3 Reporting the Activity Date of This ADC				[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 65.80% (Day 65)	Negative AXL expression (AXL-)
Method Description	In vivo antitumor activity of ADCT-601 in BRCA1-mutated ovarian cancer PDX model. Single-dose (0.15 mg/kg,q.d.) ADCT-601 in combination with olaparib (50 mg/kg) and isotype-control ADC (B12-PL1601) were administered intravenously (day 1) to treatment groups of 8 mice.
In Vivo Model	BRCA1-mutated ovarian cancer PDX model (PDX: CTG-0703)
Experiment 4 Reporting the Activity Date of This ADC				[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 68.70% (Day 30)	Negative AXL expression (AXL-)
Method Description	In vivo antitumor activity of ADCT-601 in a MMAE-resistant NCI-H1299 NSCLC model. Single-dose (0.50 mg/kg,q.d.) ADCT-601 and isotype-control ADC (B12-PL1601) were administered intravenously (day 1) to treatment groups of 8 mice.
In Vivo Model	MMAE-resistant non-small cell lung cancer PDX model (PDX: NCI-H1299)
Experiment 5 Reporting the Activity Date of This ADC				[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 72.10% (Day 30)	Positive AXL expression (AXL+++/++; 88,000 copy number)
Method Description	In vivo antitumor activity of ADCT-601 in a MMAE-resistant NCI-H1299 NSCLC model. Single-dose (1.00 mg/kg,q.d.) ADCT-601 and isotype-control ADC (B12-PL1601) were administered intravenously (day 1) to treatment groups of 8 mice.
In Vivo Model	MMAE-resistant non-small cell lung cancer PDX model (PDX: NCI-H1299)
Experiment 6 Reporting the Activity Date of This ADC				[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 84.90% (Day 21)	Positive AXL expression (AXL+++/++; 88,000 copy number)
Method Description	The antitumor activity of ADCT-601 was tested in a range of human solid tumor xenograft models covering multiple indications. Single-dose (0.15 mg/kg,q.d.). ADCT-601 and isotype-control ADC (B12-PL1601) were administered intravenously (day 1) to treatment groups of 8 mice.
In Vivo Model	Pancreatic cancer PDX model (PDX: PAXF1657)
Experiment 7 Reporting the Activity Date of This ADC				[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 96.90% (Day 21)	Positive AXL expression (AXL+++/++; 88,000 copy number)
Method Description	The antitumor activity of ADCT-601 was tested in a range of human solid tumor xenograft models covering multiple indications. Single-dose (0.30 mg/kg,q.d.). ADCT-601 and isotype-control ADC (B12-PL1601) were administered intravenously (day 1) to treatment groups of 8 mice.
In Vivo Model	Pancreatic cancer PDX model (PDX: PAXF1657)
Experiment 8 Reporting the Activity Date of This ADC				[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 98.50% (Day 51)	Positive AXL expression (AXL+++/++; 36,000 copy number)
Method Description	The antitumor activity of ADCT-601 was tested in a range of human solid tumor xenograft models covering multiple indications. Single-dose (1 mg/kg,q.d.) 0.ADCT-601 and isotype-control ADC (B12-PL1601) were administered intravenously (day 1) to treatment groups of 8 mice.
In Vivo Model	Esophageal caner PDX model (PDX: ES0195)

Discovered Using Cell Line-derived Xenograft Model

Click To Hide/Show 4 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 69.40% (Day 60)	Positive AXL expression (AXL+++/++)
Method Description	The antitumor activity of ADCT-601 was tested in a range of human solid tumor xenograft models covering multiple indications. Single-dose (0.30 mg/kg,q.d.). ADCT-601 and isotype-control ADC (B12-PL1601) were administered intravenously (day 1) to treatment groups of 8 mice.
In Vivo Model	kidney cancer CDX model
In Vitro Model	Renal cell carcinoma	SN12C cells		CVCL_1705
Experiment 2 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 86.20% (Day 60)	Positive AXL expression (AXL+++/++)
Method Description	The antitumor activity of ADCT-601 was tested in a range of human solid tumor xenograft models covering multiple indications. Single-dose (0.60 mg/kg,q.d.). ADCT-601 and isotype-control ADC (B12-PL1601) were administered intravenously (day 1) to treatment groups of 8 mice.
In Vivo Model	kidney cancer CDX model
In Vitro Model	Renal cell carcinoma	SN12C cells		CVCL_1705
Experiment 3 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 97.60% (Day 23)	Positive AXL expression (AXL+++/++)
Method Description	The antitumor activity of ADCT-601 was tested in a range of human solid tumor xenograft models covering multiple indications. Single-dose (1.00 mg/kg,q.d.). ADCT-601 and isotype-control ADC were administered intravenously (day 1) to treatment groups of 10 mice.
In Vivo Model	Triple-negative breast cancer CDX model
In Vitro Model	Breast adenocarcinoma	MDA-MB-231 cells		CVCL_0062
Experiment 4 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 98.50% (Day 60)	Positive AXL expression (AXL+++/++)
Method Description	The antitumor activity of ADCT-601 was tested in a range of human solid tumor xenograft models covering multiple indications. Single-dose (1.00 mg/kg,q.d.). ADCT-601 and isotype-control ADC (B12-PL1601) were administered intravenously (day 1) to treatment groups of 8 mice.
In Vivo Model	Kidney cancer CDX model
In Vitro Model	Renal cell carcinoma	SN12C cells		CVCL_1705

Revealed Based on the Cell Line Data

Click To Hide/Show 9 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.02 nM	Positive AXL expression (AXL+++/++; 46,000 copy number)
Method Description	In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO₂-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines. Click to Show/Hide
In Vitro Model	Lung adenocarcinoma	SK-LU-1 cells		CVCL_0629
Experiment 2 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.11 nM	Positive AXL expression (AXL+++/++; 88,000 copy number)
Method Description	In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO₂-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines. Click to Show/Hide
In Vitro Model	Ovarian serous cystadenocarcinoma	SK-OV-3 cells		CVCL_0532
Experiment 3 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.35 nM	Positive AXL expression (AXL+++/++; 79,000 copy number)
Method Description	In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO₂-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines. Click to Show/Hide
In Vitro Model	Breast adenocarcinoma	MDA-MB-231 cells		CVCL_0062
Experiment 4 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.47 nM	Positive AXL expression (AXL+++/++; 24,000 copy number)
Method Description	In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO₂-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines. Click to Show/Hide
In Vitro Model	Pancreatic ductal adenocarcinoma	PANC-1 cells		CVCL_0480
Experiment 5 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.59 nM	Positive AXL expression (AXL+++/++; 23,000 copy number)
Method Description	In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO₂-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines. Click to Show/Hide
In Vitro Model	Glioblastoma	A-172 cells		CVCL_0131
Experiment 6 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.83 nM	Positive AXL expression (AXL+++/++; 79,000 copy number)
Method Description	In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO₂-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines. Click to Show/Hide
In Vitro Model	Renal cell carcinoma	SN12C cells		CVCL_1705
Experiment 7 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	2.20 nM	Positive AXL expression (AXL+++/++; 20,000 copy number)
Method Description	In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO₂-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines. Click to Show/Hide
In Vitro Model	Lung large cell carcinoma	NCI-H1299 cells		CVCL_0060
Experiment 8 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	9.29 nM	Positive AXL expression (AXL+++/++; 79,000 copy number)
Method Description	In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO₂-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines. Click to Show/Hide
In Vitro Model	Breast adenocarcinoma	MDA-MB-361 cells		CVCL_0620
Experiment 9 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	14.62 nM	Positive AXL expression (AXL+++/++; 36,000 copy number)
Method Description	In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO₂-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines. Click to Show/Hide
In Vitro Model	ALK-positive anaplastic large cell lymphoma	Karpas-299 cells		CVCL_1324

References

Ref 1	Preclinical Development of ADCT-601, a Novel Pyrrolobenzodiazepine Dimer-based Antibody-drug Conjugate Targeting AXL-expressing Cancers. Mol Cancer Ther. 2022 Apr 1;21(4):582-593.

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Correspondence

Prof. Feng ZHU (zhufeng@zju.edu.cn)

Prof. Xiaowu DONG (dongxw@zju.edu.cn)

Prof. Luo FANG (fangluo@zjcc.org.cn)