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Published on: March 6, 2018
Novel Redirected T-Cell Immunotherapies for Advanced Prostate Cancer
Tanya B Dorff1, Vivek Narayan2, Stephen J Forman3
1Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, California.
Abstract:
Immunotherapy has failed to achieve durable remissions in advanced prostate cancer patients. More potent T-cell-redirecting strategies may be needed to overcome the immunologically exclusive and suppressive tumor microenvironment. Clinical trials are underway, seeking to define the optimal target for T-cell redirection, such as PSMA, PSCA, or STEAP-1, as well as the optimal strategy, with CAR or bispecific antibodies. As results continue to emerge from these trials, understanding differential toxicity and efficacy of these therapies based on their targets and functional modifications will be key to advancing these promising therapies toward clinical practice. This review provides a unique depth and breadth of perspective regarding the diverse immunotherapy strategies currently under clinical investigation for men with advanced prostate cancer.
Insights
Immunotherapy shows limited success in advanced prostate cancer. New T-cell-redirecting strategies targeting PSMA, PSCA, or STEAP-1 are being investigated to improve durable remissions.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Advanced prostate cancer (PCa) has historically shown poor response to immunotherapy, necessitating novel treatment approaches.
- The tumor microenvironment in advanced PCa is often immunosuppressive and exclusive, hindering effective anti-tumor immune responses.
- Durable remissions remain a significant challenge for patients with advanced prostate cancer undergoing immunotherapy.
Purpose of the Study:
- To review and analyze diverse immunotherapy strategies currently under clinical investigation for advanced prostate cancer.
- To explore the potential of T-cell-redirecting therapies in overcoming the challenges posed by the PCa tumor microenvironment.
- To provide a comprehensive perspective on emerging immunotherapeutic targets and strategies for advanced PCa.
Main Methods:
- Review of current clinical trials investigating T-cell-redirecting strategies in advanced prostate cancer.
- Analysis of potential targets such as Prostate-Specific Membrane Antigen (PSMA), Prostate Stem Cell Antigen (PSCA), and STEAP-1.
- Evaluation of different therapeutic modalities including Chimeric Antigen Receptor (CAR) T-cells and bispecific antibodies.
Main Results:
- Multiple T-cell-redirecting strategies are in clinical trials for advanced prostate cancer.
- Key targets under investigation include PSMA, PSCA, and STEAP-1.
- Both CAR T-cell therapy and bispecific antibodies are being explored as optimal strategies.
Conclusions:
- More potent T-cell-redirecting strategies are crucial for achieving durable remissions in advanced prostate cancer.
- Understanding the differential toxicity and efficacy based on targets and modifications is essential for clinical advancement.
- Emerging immunotherapies hold promise for improving outcomes in men with advanced prostate cancer.
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