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Immunotherapy for the treatment of prostate cancer

Abstract

Failure of immune surveillance has a prominent role in tumorigenesis. Cancerous cells can evade T-cell responses to tumor-associated antigens by multiple mechanisms. Active immunotherapy aims to stimulate the immune response against cancer cells. Unlike normal prostate tissue, prostate cancer is not ignored by the immune system, as shown by the presence of tumor infiltrating lymphocytes. This characteristic renders prostate cancer particularly suitable for immunotherapy. The existence of well-defined antigens, largely limited to prostate tissue, allows prostate cancer cells to be targeted without the risk of systemic autoimmune reactions, as autoimmunity specifically directed at the prostate is the goal of prostate cancer immunotherapy. Active immunotherapy directed towards prostate cancer can be conducted using multiple strategies, involving dendritic cells, whole-cell vaccines, viral vectors, DNA-based and peptide-based agents, as well as immunostimulatory agents. The only FDA-approved immunotherapy for prostate cancer is the dendritic-cell-based agent Sipuleucel-T, which yielded an advantage in overall survival, but not in progression-free survival in a phase III trial. We present the clinical developments in the field of immunotherapy and critically analyze methodological issues related to the evaluation of tumor responses to immunotherapy, trial design, and surrogate end points.

Key Points

  • The existence of well-defined antigens provides a strong biological rationale for immunotherapy of prostate cancer and encouraging treatment results have been achieved in the past year

  • Active immunotherapy stimulates an immune response against cancer tissue and includes the use of autologous dendritic-cell-based, DNA-based, and peptide-based agents, whole-cell vaccines, viral vectors, and immunostimulatory substances

  • Sipuleucel-T is the only FDA-approved active immunotherapy; in a phase III trial conducted in patients with metastatic castration-resistant prostate cancer (CRPC), Sipuleucel-T improved overall survival by 4 months compared with placebo

  • PROSTVAC®–VF/TRICOM consists of Vaccinia and Fowlpox viral vectors, and enhanced survival of patients with CRPC by 8.5 months in a placebo-controlled phase II trial

  • Neither Sipuleucel-T, nor PROSTVAC®–VF/TRICOM, however, improved progression-free survival or the prostate-specific-antigen response rate in the respective phase II and phase III trials

  • The lack of positive effects when using these standard surrogate end points underlines the need for innovative methodological criteria that assess efficacy of immunotherapy in clinical trials

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Figure 1: Mechanism of action of Sipuleucel-T.
Figure 2: Mechanism of action of DNA-based immunotherapy.

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Authors and Affiliations

Authors

Contributions

G. Di Lorenzo and C. Buonerba researched the data and wrote the article. All authors provided substantial contributions to the discussion of content and reviewed/edited the manuscript before submission.

Corresponding author

Correspondence to Giuseppe Di Lorenzo.

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Competing interests

P. Kantoff declares that he was a consultant for Dendreon Corporation and BN Immunotherapeutics. G. Di Lorenzo and C. Buonerba declare no competing interests.

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Di Lorenzo, G., Buonerba, C. & Kantoff, P. Immunotherapy for the treatment of prostate cancer. Nat Rev Clin Oncol 8, 551–561 (2011). https://doi.org/10.1038/nrclinonc.2011.72

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