Antibody Information
General Information of This Antibody
| Antibody ID | ANI0CDJLA |
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| Antibody Name | J591 |
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| Organization | Weill Cornell Medical |
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| Indication | Prostate cancer |
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| Synonyms |
HUJ-591; HUJ591-GS; Rosopatamab
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| Antibody Type | Monoclonal antibody (mAb) |
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| Antibody Subtype | Chimeric IgG1-kappa |
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| Antigen Name | Glutamate carboxypeptidase 2 (FOLH1) |
Antigen Info | ||||
| ChEMBI ID | ||||||
| Click to Show/Hide the Sequence Information of This Antibody | ||||||
| Heavy Chain Sequence |
EVQLVQSGPEVKKPGATVKISCKTSGYTFTEYTIHWVKQAPGKGLEWIGNINPNNGGTTY
NQKFEDKATLTVDKSTDTAYMELSSLRSEDTAVYYCAAGWNFDYWGQGTLLTVSSASTKG PSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSL SSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFL FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNV FSCSVMHEALHNHYTQKSLSLSPGK Click to Show/Hide
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| Heavy Chain Varible Domain |
EVQLVQSGPEVKKPGATVKISCKTSGYTFTEYTIHWVKQAPGKGLEWIGNINPNNGGTTY
NQKFEDKATLTVDKSTDTAYMELSSLRSEDTAVYYCAAGWNFDYWGQGTLLTVSS Click to Show/Hide
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| Heavy Chain Constant Domain 1 |
ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS
GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKV Click to Show/Hide
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| Heavy Chain Constant Domain 2 |
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK
PREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK Click to Show/Hide
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| Heavy Chain Constant Domain 3 |
GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS
DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK Click to Show/Hide
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| Heavy Chain Hinge Region |
EPKSCDKTHTCPPCP
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| Heavy Chain CDR 1 |
GYTFTEYT
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| Heavy Chain CDR 2 |
INPNNGGT
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| Heavy Chain CDR 3 |
AAGWNFDY
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| Light Chain Sequence |
DIQMTQSPSSLSTSVGDRVTLTCKASQDVGTAVDWYQQKPGPSPKLLIYWASTRHTGIPS
RFSGSGSGTDFTLTISSLQPEDFADYYCQQYNSYPLTFGPGTKVDIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC Click to Show/Hide
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| Light Chain Varible Domain |
DIQMTQSPSSLSTSVGDRVTLTCKASQDVGTAVDWYQQKPGPSPKLLIYWASTRHTGIPS
RFSGSGSGTDFTLTISSLQPEDFADYYCQQYNSYPLTFGPGTKVDIK Click to Show/Hide
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| Light Chain Constant Domain |
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD
SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC Click to Show/Hide
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| Light Chain CDR 1 |
QDVGTA
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| Light Chain CDR 2 |
WAS
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| Light Chain CDR 3 |
QQYNSYPLT
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Each Antibody-drug Conjugate Related to This Antibody
Full Information of The Activity Data of The ADC(s) Related to This Antibody
MEDI3726 [Phase 1 (discontinued)]
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Progression Free Survival |
3.9 months
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| Patients Enrolled |
Eligible participants must be ≥18 years with metastatic castration-resistant prostate cancer (mCRPC) progressing after abiraterone/enzalutamide therapy. Key exclusions include prior PSMA-directed therapies, recent anti-cancer treatments (within 21 days), brain metastases requiring treatment, radiation affecting >25% marrow-bearing bone, or history of significant peripheral vasculopathies.
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| Administration Dosage |
As of Sept 27 2019, 33 pts received MEDI3726. Median age was 71.0 yr. Median number of prior regimens was 4. Median follow-up was 5.4 mo. Drug-related AEs occurred in 30 (90.9%), being grade 3/4 in 15 (45.5%), serious in 11 (33.3%) and causing discontinuation in 13 (39.4%). There were no drug-related deaths. One pt at 0.3 mg/kg had a DLT of Grade 3 thrombocytopenia. No MTD was identified per mTPI; the MAD was 0.3 mg/kg.
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| Related Clinical Trial | |||||
| NCT Number | NCT02991911 | Clinical Status | PHASE1 | ||
| Clinical Description |
A Phase 1/1b Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI3726 in Subjects With Metastatic Castration Resistant Prostate Cancer Who Have Received Prior Treatment With Abiraterone or Enzalutamide.
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| Primary Endpoint |
The study evaluates safety through monitoring adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs) from informed consent through 90 days post-treatment, with laboratory parameters, vital signs, and ECG changes assessed up to 21-90 days after last MEDI3726 dose.
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| Other Endpoint |
Efficacy is measured via RECIST v1.1 response, PSA50 reduction, and circulating tumor cell (CTC) conversion over 12-90 days. Pharmacokinetic analysis includes MEDI3726 plasma concentration, Cmax, AUC, clearance, and half-life, alongside immunogenicity assessment through anti-drug antibodies (ADAs) during the 90-day follow-up period.
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| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Overall suvival (OS) |
10.6 months
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| Patients Enrolled |
Eligible participants must be ≥18 years with metastatic castration-resistant prostate cancer (mCRPC) progressing after abiraterone/enzalutamide therapy. Key exclusions include prior PSMA-directed therapies, recent anti-cancer treatments (within 21 days), brain metastases requiring treatment, radiation affecting >25% marrow-bearing bone, or history of significant peripheral vasculopathies.
Click to Show/Hide
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| Administration Dosage |
As of Sept 27 2019, 33 pts received MEDI3726. Median age was 71.0 yr. Median number of prior regimens was 4. Median follow-up was 5.4 mo. Drug-related AEs occurred in 30 (90.9%), being grade 3/4 in 15 (45.5%), serious in 11 (33.3%) and causing discontinuation in 13 (39.4%). There were no drug-related deaths. One pt at 0.3 mg/kg had a DLT of Grade 3 thrombocytopenia. No MTD was identified per mTPI; the MAD was 0.3 mg/kg.
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| Related Clinical Trial | |||||
| NCT Number | NCT02991911 | Clinical Status | PHASE1 | ||
| Clinical Description |
A Phase 1/1b Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI3726 in Subjects With Metastatic Castration Resistant Prostate Cancer Who Have Received Prior Treatment With Abiraterone or Enzalutamide.
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| Primary Endpoint |
The study evaluates safety through monitoring adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs) from informed consent through 90 days post-treatment, with laboratory parameters, vital signs, and ECG changes assessed up to 21-90 days after last MEDI3726 dose.
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| Other Endpoint |
Efficacy is measured via RECIST v1.1 response, PSA50 reduction, and circulating tumor cell (CTC) conversion over 12-90 days. Pharmacokinetic analysis includes MEDI3726 plasma concentration, Cmax, AUC, clearance, and half-life, alongside immunogenicity assessment through anti-drug antibodies (ADAs) during the 90-day follow-up period.
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| Experiment 3 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Composite Response Rate (RR) |
12.10%
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| Patients Enrolled |
Patients with metastatic castration-resistant prostate cancer after disease progression on abiraterone and/or enzalutamide and taxane-based chemotherapy.
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| Administration Dosage |
Administered at 0.015-0.30 mg/kg intravenously every 3 weeks until disease progression/unacceptable toxicity; The MTD was not identified; the MAD was 0.30 mg/kg.
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| Related Clinical Trial | |||||
| NCT Number | NCT02991911 | Clinical Status | Phase 1 | ||
| Clinical Description |
A phase 1/1b multicenter, open-label, dose-escalation and dose-expansion study to evaluate the safety, pharmacokinetics, immunogenicity, and antitumor activity of MEDI3726 in subjects with metastatic castration resistant prostate cancer who have received prior treatment with abiraterone or enzalutamide.
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Discovered Using Cell Line-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 15.86% | High PSMA expression (PSMA+++; 250,494 PSMA molecules/cell) | ||
| Method Description |
The inhibitory activity of MEDI3726 against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.33 mg/kg MEDI3726.
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| In Vivo Model | PC-3 CDX model | ||||
| In Vitro Model | Prostate carcinoma | PC-3 cells | CVCL_0035 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 36.17% | Moderate PSMA expression (PSMA++; 43,766 PSMA molecules/cell) | ||
| Method Description |
The inhibitory activity of MEDI3726 against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.11 mg/kg MEDI3726.
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| In Vivo Model | PC-3 CDX model | ||||
| In Vitro Model | Prostate carcinoma | LNCaP cells | CVCL_0395 | ||
| Experiment 3 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 45.68% | High PSMA expression (PSMA+++; 250,494 PSMA molecules/cell) | ||
| Method Description |
The inhibitory activity of MEDI3726 against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 1 mg/kg MEDI3726.
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| In Vivo Model | PC-3 CDX model | ||||
| In Vitro Model | Prostate carcinoma | PC-3 cells | CVCL_0035 | ||
| Experiment 4 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 68.20% | Moderate PSMA expression (PSMA++; 43,766 PSMA molecules/cell) | ||
| Method Description |
The inhibitory activity of MEDI3726 against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.33 mg/kg MEDI3726.
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| In Vivo Model | PC-3 CDX model | ||||
| In Vitro Model | Prostate carcinoma | LNCaP cells | CVCL_0395 | ||
| Experiment 5 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 76.95% | High PSMA expression (PSMA+++; 250,494 PSMA molecules/cell) | ||
| Method Description |
The inhibitory activity of MEDI3726 against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 1 mg/kg MEDI3726.
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| In Vivo Model | PC-3 CDX model | ||||
| In Vitro Model | Prostate carcinoma | LNCaP cells | CVCL_0395 | ||
| Experiment 6 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 93.55% | Negative PSMA expression (PSMA-) | ||
| Method Description |
The inhibitory activity of MEDI3726 against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.33 mg/kg MEDI3726.
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| In Vivo Model | PC-3 CDX model | ||||
| In Vitro Model | Prostate carcinoma | 22RV1 cells | CVCL_1045 | ||
| Experiment 7 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 98.71% | Negative PSMA expression (PSMA-) | ||
| Method Description |
The inhibitory activity of MEDI3726 against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 1 mg/kg MEDI3726.
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| In Vivo Model | PC-3 CDX model | ||||
| In Vitro Model | Prostate carcinoma | 22RV1 cells | CVCL_1045 | ||
YC1667 [Investigative]
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [4] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) |
5.623 ng/mL
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Positive PSMA expression (PSMA+++/++) | ||
| Method Description |
ADCs (10x the final top concentration) was tested in C4-2B cells for 3 days.
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| In Vitro Model | Prostate carcinoma | LNCaP cells | CVCL_0395 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [4] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) |
11.16 ng/mL
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Positive PSMA expression (PSMA+++/++) | ||
| Method Description |
ADCs (10x the final top concentration) was tested in LNCap cells for 3 days.
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| In Vitro Model | Prostate carcinoma | LNCaP cells | CVCL_0395 | ||
YC1663 [Investigative]
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [4] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) |
9.269 ng/mL
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Positive PSMA expression (PSMA+++/++) | ||
| Method Description |
ADCs (10x the final top concentration) was tested in LNCap cells for 3 days.
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| In Vitro Model | Prostate carcinoma | LNCaP cells | CVCL_0395 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [4] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) |
9.269 ng/mL
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Positive PSMA expression (PSMA+++/++) | ||
| Method Description |
ADCs (10x the final top concentration) was tested in C4-2B cells for 3 days.
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| In Vitro Model | Prostate carcinoma | LNCaP cells | CVCL_0395 | ||
References