Review article
Immunotherapy for castration-resistant prostate cancer: Progress and new paradigms,☆☆

https://doi.org/10.1016/j.urolonc.2014.10.009Get rights and content
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Abstract

Background

The approval of sipuleucel-T in conjunction with data from other immunotherapeutic trials for prostate cancer and other solid tumors demonstrates the potential of harnessing the patient׳s immune system for long-term survival. Thus, a range of therapeutic approaches are under evaluation. This review describes the rationale for immunotherapy for prostate cancer, summarizes the approaches under evaluation, and discusses sequencing options for immunotherapy in the current treatment paradigm.

Design

References for this review were identified through searches of PubMed with the search terms “prostate cancer,” “immune system,” “vaccine,” “immunotherapy,” and “T cells.” Articles were also identified through searches of the authors׳ own files. The final reference list was generated based on originality and relevance.

Results

The immune system can recognize and respond to prostate tumor antigens, effected through tumor-associated antigens and tumor infiltration of immune effector cells. However, evidence also suggests that prostate tumors are adept at escaping immunological recognition, thus hypothesizing multiple therapeutic strategies. Therapeutic approaches could include vaccination and modulation of T-cell function via the blockade of checkpoint receptors such as cytotoxic T-lymphocyte antigen-4 and programmed death 1. In phase III trials, sipuleucel-T improved overall survival for an M1 patient population with castration-resistant prostate cancer and ipilimumab also did so when given after radiotherapy in a subset of better risk patients. In randomized phase II trials, prostate-specific antigen-TRICOM improved overall survival and tasquinimod improved progression-free survival.

Conclusion

Although immunotherapy has the potential to affect advanced prostate cancer, additional research is needed to (1) identify predictive or surrogate markers of activity, (2) understand which agents are clinically effective alone or in combination with other therapies, and (3) define the optimal timing for an immunotherapy to achieve maximal benefit.

Keywords

Prostate cancer
Immunotherapy
Vaccine
T cell
Immune system

Cited by (0)

The authors take full responsibility for the content of this publication and confirm that it reflects their viewpoint and medical expertise. The authors also wish to acknowledge Rebecca Turner, StemScientific, funded by Bristol-Myers Squibb, for providing writing and editorial support. Neither Bristol-Myers Squibb nor StemScientific influenced the content of the manuscript, nor did the authors receive financial compensation for authoring the manuscript.

☆☆

D.Q. discloses payment for scientific advisory board participation from Amgen, Astellas, Bayer Healthcare, BMS, Dendreon, Fresenius Kabi, Millennium Takeda, Novartis, Janssen, Medivation, and Teva. He has received clinical trial funding from the National Cancer Institute, Millennium Takeda, GlaxoSmithKline, and Sanofi-Aventis. N.S. discloses involvement in research or consultancy for Algeta, Amgen, Bayer, Dendreon, Genomic Health, Myriad, Janssen, Medivation, Pfizer, and Sanofi-Aventis. S.E. discloses research finding from Astellas, AstraZeneca, and Takeda. K.F. discloses participation in advisory board or speaker for Dendreon, CureVac, Janssen, Astellas, Amgen, Bayer, Sanofi, Novartis, and Bristol-Myers Squibb.