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Updated: Jul 5, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Clinical trials of cancer therapies targeting prostate-specific membrane antigen
William C Olson1, Warren D W Heston, Ayyappan K Rajasekaran
1PSMA Development Company, LLC, Tarrytown, NY, USA.
Abstract:
Prostate cancer is the most common non-cutaneous cancer of men in the United States and represents their second-leading cause of cancer-related death. Metastatic disease is largely resistant to conventional chemotherapies, and targeted therapies are urgently needed. Prostate-specific membrane antigen (PSMA) is a prototypical cell-surface marker of prostate cancer. PSMA is an integral, non-shed, type 2 membrane protein with abundant and nearly universal expression in prostate carcinoma, but has limited extra-prostatic expression. In addition, PSMA is expressed in the neovasculature of other solid tumors. These findings have spurred development of PSMA-targeted therapies for cancer, and first-generation products have entered clinical testing. Vaccine approaches have included recombinant protein, nucleic acid and cell-based strategies, and anti-PSMA immune responses have been demonstrated in the absence of significant toxicity. Therapy with drug-conjugated and radiolabeled antibodies has yielded objective clinical responses as measured by reductions in serum prostate-specific antigen and/or imageable tumor volume. However, responses were observed in a minor fraction of patients and at doses near the maximum tolerated dose. Overall, these initial studies have provided measured proof of concept for PSMA-based therapies, and second-generation antibody and vaccine products may hold the key to exploit PSMA for molecularly targeted therapy of prostate and other cancers.
Insights
Prostate-specific membrane antigen (PSMA) targeted therapies show promise for advanced prostate cancer. While initial treatments yielded modest results, second-generation therapies offer potential for improved efficacy in treating prostate and other cancers.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Targeted Therapy
Background:
- Prostate cancer is a leading cause of cancer death in men, with metastatic disease often resistant to chemotherapy.
- Prostate-specific membrane antigen (PSMA) is highly expressed on prostate cancer cells, making it a promising therapeutic target.
- PSMA is also found in the neovasculature of other solid tumors, suggesting broader therapeutic potential.
Purpose of the Study:
- To review the development and clinical progress of PSMA-targeted therapies for cancer.
- To evaluate the efficacy and limitations of first-generation PSMA-based treatments.
- To highlight the potential of second-generation PSMA-targeted agents.
Main Methods:
- Review of clinical studies involving PSMA-targeted vaccines (recombinant protein, nucleic acid, cell-based).
- Analysis of outcomes from therapies using drug-conjugated and radiolabeled antibodies targeting PSMA.
- Assessment of clinical responses, including serum PSA reduction and tumor volume changes.
Main Results:
- PSMA-targeted vaccines demonstrated anti-tumor immune responses without significant toxicity.
- Antibody-based therapies showed objective clinical responses in a subset of patients.
- Responses were often observed at near-maximum tolerated doses, indicating room for improvement.
Conclusions:
- First-generation PSMA-targeted therapies provide proof of concept for their utility in cancer treatment.
- Second-generation antibody and vaccine products are expected to enhance the efficacy of PSMA-based therapies.
- Targeting PSMA holds significant potential for molecularly targeted therapy in prostate and other cancers.
