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Updated: May 30, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Prostate-specific membrane antigen-based therapeutics
Naveed H Akhtar1, Orrin Pail, Ankeeta Saran
1Division of Hematology and Medical Oncology, Weill Cornell Medical College, 525 E. 68th Street, Box 403, New York, NY 10065, USA.
Abstract:
Prostate cancer (PC) is the most common noncutaneous malignancy affecting men in the US, leading to significant morbidity and mortality. While significant therapeutic advances have been made, available systemic therapeutic options are lacking. Prostate-specific membrane antigen (PSMA) is a highly-restricted prostate cell-surface antigen that may be targeted. While initial anti-PSMA monoclonal antibodies were suboptimal, the development of monoclonal antibodies such as J591 which are highly specific for the external domain of PSMA has allowed targeting of viable, intact prostate cancer cells. Radiolabeled J591 has demonstrated accurate and selective tumor targeting, safety, and efficacy. Ongoing studies using anti-PSMA radioimmunotherapy with (177)Lu-J591 seek to improve the therapeutic profile, select optimal candidates with biomarkers, combine with chemotherapy, and prevent or delay the onset of metastatic disease for men with biochemical relapse. Anti-PSMA monoclonal antibody-drug conjugates have also been developed with completed and ongoing early-phase clinical trials. As PSMA is a selective antigen that is highly overexpressed in prostate cancer, anti-PSMA-based immunotherapy has also been studied and utilized in clinical trials.
Insights
Targeting prostate cancer (PC) with advanced anti-prostate-specific membrane antigen (PSMA) therapies, including radioimmunotherapy and antibody-drug conjugates, shows promise for improving treatment outcomes in men with advanced disease.
Area of Science:
- Oncology
- Immunotherapy
- Radiopharmaceuticals
Background:
- Prostate cancer (PC) is a leading cause of cancer-related death in men, with limited systemic treatment options for advanced stages.
- Prostate-specific membrane antigen (PSMA) is a highly specific target overexpressed on prostate cancer cells.
- Previous anti-PSMA antibodies were less effective; newer J591 antibodies target the external domain of PSMA on viable cells.
Purpose of the Study:
- To review the development and clinical application of anti-PSMA therapies for prostate cancer.
- To highlight the potential of novel immunotherapies and radioimmunoconjugates in treating advanced prostate cancer.
- To explore strategies for optimizing patient selection and treatment combinations.
Main Methods:
- Review of clinical trials and preclinical studies involving anti-PSMA monoclonal antibodies, including J591.
- Analysis of radiolabeled J591 (radioimmunotherapy) and anti-PSMA antibody-drug conjugates.
- Investigation of PSMA-targeted immunotherapy approaches.
Main Results:
- Radiolabeled J591 demonstrates accurate tumor targeting, safety, and efficacy in clinical studies.
- Ongoing trials with (177)Lu-J591 aim to enhance therapeutic profiles and patient selection.
- Anti-PSMA antibody-drug conjugates are in early-phase clinical trials, showing therapeutic potential.
Conclusions:
- Anti-PSMA therapies, particularly radioimmunotherapy with J591 and antibody-drug conjugates, represent a promising advancement in prostate cancer treatment.
- Targeting PSMA offers a highly specific approach to combatting prostate cancer, including in cases of biochemical relapse.
- Future research focuses on optimizing these therapies, combining them with chemotherapy, and preventing metastatic progression.
