Antibody Information

General Information of This Antibody
Antibody ID
ANI0FQFZL
Antibody Name
Sirtratumab
Organization
Agensys, Inc.
Indication
Solid tumors
Synonyms
AGS-15C; AGS15C; Ha15-10ac12; Ha15-10ac12.1
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Antibody Type
Monoclonal antibody (mAb)
Antibody Subtype
Humanized IgG2-kappa
Antigen Name
SLIT and NTRK-like protein 6 (SLITRK6)
  Antigen Info 
Click to Show/Hide the Sequence Information of This Antibody
Heavy Chain Sequence
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVIWYDGSNQYY
ADSVKGRFTISRDNSKNTLFLQMHSLRAEDTAVYYCARGLTSGRYGMDVWGQGTTVTVSS
ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS
GLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVF
LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFR
VVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKN
QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
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Heavy Chain Varible Domain
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVIWYDGSNQYY
ADSVKGRFTISRDNSKNTLFLQMHSLRAEDTAVYYCARGLTSGRYGMDVWGQGTTVTVSS
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Heavy Chain Constant Domain 1
ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS
GLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTV
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Heavy Chain Constant Domain 2
APPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP
REEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTK
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Heavy Chain Constant Domain 3
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDS
DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
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Heavy Chain Hinge Region
ERKCCVECPPCP
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Heavy Chain CDR 1
GFTFSSYG
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Heavy Chain CDR 2
IWYDGSNQ
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Heavy Chain CDR 3
ARGLTSGRYGMDV
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Light Chain Sequence
DIVMTQSPLSLPVTPGEPASISCRSSQSLLLSHGFNYLDWYLQKPGQSPQLLIYLGSSRA
SGVPDRFSGSGSGTDFTLKISRVEAEDVGLYYCMQPLQIPWTFGQGTKVEIKRTVAAPSV
FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
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Light Chain Varible Domain
DIVMTQSPLSLPVTPGEPASISCRSSQSLLLSHGFNYLDWYLQKPGQSPQLLIYLGSSRA
SGVPDRFSGSGSGTDFTLKISRVEAEDVGLYYCMQPLQIPWTFGQGTKVEIK
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Light Chain Constant Domain
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD
SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
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Light Chain CDR 1
QSLLLSHGFNY
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Light Chain CDR 2
LGS
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Light Chain CDR 3
MQPLQIPWT
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The Activity Data of This Antibody
Antibody Activity Information 1 [1]
Dissociation Constant (Kd)
15
pM
SW780 cells CVCL_1728 
Antigen Expression Positive SLITRK6 expression (SLITRK6+++/++)
Antibody Function Confirm the effect of the drug conjugation with the anti-SLITRK6 mAb and ADC on binding activity to cell line.
Antibody Antigen Binding Assay FACS analysis to determine maximum binding (Bmax) and affinity of ASG-15ME (ADC) and AGS-15C (unconjugated mAb). For the assay, antibodies were serially diluted and incubated with SW-780 cells (50,000 cells/well) at a final concentration of 40.0 to 0.00067 nmol/L and added to the SW-780 cells for overnight incubation at 4C.
Each Antibody-drug Conjugate Related to This Antibody
Full Information of The Activity Data of The ADC(s) Related to This Antibody
Sirtratumab vedotin [Phase 1]
 ADC Info 
Identified from the Human Clinical Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [2]
Efficacy Data Objective Response Rate (ORR)
13.00% (0.50 mg/kg)
29.00% (0.75 mg/kg)
40.00% (1.00 mg/kg)
40.00% (1.25 mg/kg)
High SLITRK6 expression (SLITRK6+++; IHC H-score=230)
Patients Enrolled
Metastatic uroepithelial carcinoma (mUC) patients unselected for SLITRK6 expression (determined by an IHC assay) and previously treated with 1 prior chemo regimen or unfit for cisplatin.
Administration Dosage
Administered IV weekly for 3 out of every 4 weeks.
Related Clinical Trial
NCT Number NCT01963052  Clinical Status Phase 1
Clinical Description
A phase 1 study of the safety and pharmacokinetics of escalating doses of AGS15E given as monotherapy in subjects with metastatic urothelial cancer.
Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 73.40% (Day 17) Moderate SLITRK6 expression (SLITRK6++; IHC H-score=185)
Method Description
PDX models were established by subcutaneous implantation of xenograft fragments (AG-B7 or AG-B8) in the flanks of SCID mice. When the tumor volume reached approximately 200 mm3,Sirtratumab Vedotin was dosed at 0.25 mg/kg,2x per week i.v in AG-B8 PDX model. The last dose was given on day 14.
In Vivo Model Bladder cancer PDX model (PDX: AG-B8)
Experiment 2 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 86.90% (Day 25) High SLITRK6 expression (SLITRK6+++; IHC H-score=280)
Method Description
PDX models were established by subcutaneous implantation of xenograft fragments (AG-B7 or AG-B8) in the flanks of SCID mice. When the tumor volume reached approximately 200 mm3,Sirtratumab Vedotin was dosed at 0.5 mg/kg,2x per week i.v in AG-B7 PDX model. The last dose was given on day 21.
In Vivo Model Bladder cancer PDX model (PDX: AG-B7)
Experiment 3 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 88.40% (Day 17) High SLITRK6 expression (SLITRK6+++; IHC H-score=250)
Method Description
PDX models were established by subcutaneous implantation of xenograft fragments (AG-B7 or AG-B8) in the flanks of SCID mice. When the tumor volume reached approximately 200 mm3,Sirtratumab Vedotin was dosed at 0.5 mg/kg,2x per week i.v in AG-B8 PDX model. The last dose was given on day 14.
In Vivo Model Bladder cancer PDX model (PDX: AG-B8)
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 88.90% (Day 30) High SLITRK6 expression (SLITRK6+++)
Method Description
CDX models were established by subcutaneous injection of between 2 and 10 million SW780, RT4 (ATCC) or NCI-H322M (NCI) cells in SCID mice. When the tumor volume reached approximately 230 mm3, a single dose of Sirtratumab Vedotin, 5 mg/kg intravenously, was administered intravenously (iv) to the mice.
In Vivo Model Bladder cancer CDX model
In Vitro Model Bladder carcinoma RT-4 cells CVCL_0036
Experiment 2 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 91.10% (Day 21) Negative SLITRK6 expression (SLITRK6-)
Method Description
CDX models were established by subcutaneous injection of between 2 and 10 million SW780, RT4 (ATCC) or NCI-H322M (NCI) cells in SCID mice. Sirtratumab Vedotin was administered twice weekly at 3 mg/kg (n = 6) starting when the tumor volume reached approximately 200 mm3.
In Vivo Model Lung cancer NCI-322M CDX model
In Vitro Model Lung cancer NCI-322M cells Homo sapiens
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 [3]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.99 nM
Method Description
ASG-15ME was tested for its ability to kill several SLITRK6-positive cell lines in vitro. The viability of CHP-212 cells treated with ASG-15ME was compared with that of target negative cells (IGR-OV1) or cells treated with an isotype control antibody to determine IC50 values.
In Vitro Model Neuroblastoma CHP-212 cells CVCL_1125
Experiment 2 Reporting the Activity Date of This ADC [3]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 10.00 uM High SLITRK6 expression (SLITRK6+++; IHC H-score=250)
Method Description
ASG-15ME was tested for its ability to kill several SLITRK6-positive cell lines in vitro. The viability of CHP-212 cells treated with ASG-15ME was compared with that of target negative cells (IGR-OV1) or cells treated with an isotype control antibody to determine IC50 values.
In Vitro Model Ovarian endometrioid adenocarcinoma IGROV-1 cells CVCL_1304
ASG-15MF [Investigative]
 ADC Info 
Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 62.90% (Day 17) High SLITRK6 expression (SLITRK6+++; IHC H-score=250)
Method Description
PDX models were established by subcutaneous implantation of xenograft fragments (AG-B7 or AG-B8) in the flanks of SCID mice. When the tumor volume reached approximately 200 mm3,ASG-15MF was dosed at 0.25 mg/kg,2x per week i.v in AG-B8 PDX model. The last dose was given on day 14.
In Vivo Model Bladder cancer PDX model (PDX: AG-B8)
Experiment 2 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 63.40% (Day 25) High SLITRK6 expression (SLITRK6+++; IHC H-score=230)
Method Description
PDX models were established by subcutaneous implantation of xenograft fragments (AG-B7 or AG-B8) in the flanks of SCID mice. When the tumor volume reached approximately 200 mm3,ASG-15MF was dosed at 0.5 mg/kg,2x per week i.v in AG-B7 PDX model. The last dose was given on day 21.
In Vivo Model Bladder cancer PDX model (PDX: AG-B7)
Experiment 3 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 80.00% (Day 17) High SLITRK6 expression (SLITRK6+++; IHC H-score=250)
Method Description
PDX models were established by subcutaneous implantation of xenograft fragments (AG-B7 or AG-B8) in the flanks of SCID mice. When the tumor volume reached approximately 200 mm3,ASG-15MF was dosed at 0.5 mg/kg,2x per week i.v in AG-B8 PDX model. The last dose was given on day 14.
In Vivo Model Bladder cancer PDX model (PDX: AG-B8)
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 35.20% (Day 21) Moderate SLITRK6 expression (SLITRK6++; IHC H-score=185)
Method Description
CDX models were established by subcutaneous injection of between 2 and 10 million SW780, RT4 (ATCC) or NCI-H322M (NCI) cells in SCID mice. ASG-15MF was administered twice weekly at 3 mg/kg (n = 6) starting when the tumor volume reached approximately 200 mm3.
In Vivo Model NCI-322M CDX model
In Vitro Model Lung cancer NCI-322M cells Homo sapiens
Experiment 2 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 81.30% (Day 30) High SLITRK6 expression (SLITRK6+++; IHC H-score=280)
Method Description
CDX models were established by subcutaneous injection of between 2 and 10 million SW780, RT4 (ATCC) or NCI-H322M (NCI) cells in SCID mice. When the tumor volume reached approximately 230 mm3, a single dose of ASG-15MF, 5 mg/kg intravenously, was administered intravenously (iv) to the mice.
In Vivo Model Bladder cancer CDX model
In Vitro Model Bladder cancer Bladder cancer cells Homo sapiens
References
Ref 1 ADC review: basic information about sirtratumab vedotin.
Ref 2 Phase 1 study of SGN-B7H4V, a novel, investigational vedotin antibodydrug conjugate directed to B7-H4, in patients with advanced solid tumors (SGNB7H4V-001, trial in progress). J Clin Oncol. 2022 40:16_suppl, TPS3155-TPS3155.
Ref 3 Development of ASG-15ME, a Novel Antibody-Drug Conjugate Targeting SLITRK6, a New Urothelial Cancer Biomarker. Mol Cancer Ther. 2016 Jun;15(6):1301-10.

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