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Personalized peptide vaccines and their relation to other therapies in urological cancer

Nature Reviews Urology volume 14, pages 501–510 (2017)Cite this article

Subjects

Key Points

  • Personalized peptide vaccines (PPVs) are an immunotherapeutic approach based on the administration of multiple cancer peptides selected from a list of candidates to complement the pre-existing immunity of a patient

  • Vaccination with an appropriately individualized selection of peptides induces stronger and more rapid antitumour immunity than inoculation of conventional peptide vaccines

  • Early-phase trials demonstrated safety and efficacy of PPVs in patients with urological cancers and randomized trials showed significant survival improvements in patients with castration-resistant prostate cancer

  • Early-phase prostate cancer trials indicate that PPV administration at an early disease stage results in increased benefits, possibly owing to limited secretion of immunosuppressive cytokines and sufficient time to develop antitumour responses in this setting

  • Combination treatment employing PPVs with chemotherapeutic agents, radiotherapy, cryoablation, or checkpoint inhibitors might be an attractive future strategy, resulting in enhanced effects owing to changes in the local immune environment

  • Future studies need to evaluate the utility of PPVs in bladder and kidney cancer, determine means to select patients who will benefit most from this treatment and optimize protocols for combination therapies involving PPVs

Abstract

Immunotherapy is an important therapeutic modality for urological cancers and several immunological agents for their treatment, such as sipuleucel-T and immune checkpoint inhibitors, have been approved by the FDA. Personalized peptide vaccines (PPVs) are an immunotherapy that uses multiple cancer peptides that are selected to complement pre-existing host immunity. Vaccination with an appropriate, individualized selection of peptides, chosen from a list of candidates, induces stronger and more rapid antitumour immunity in comparison with inoculation of conventional peptide vaccines. Phase I and phase II trials have shown that PPVs are safe and effective in urological cancers. Randomized trials in patients with castration-resistant prostate cancer showed that PPVs can significantly improve progression-free survival and overall survival. However, further studies are needed to evaluate the utility of PPVs in other urological cancers, to identify those patients who will derive the greatest benefit from this approach and to optimize the protocols for combination therapies involving PPVs.

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Figure 1: Peptide vaccination using TAA-derived short peptides.
Figure 2: Peptide vaccination using TAA-derived long peptides.

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Authors and Affiliations

  1. Department of Urology, Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105–8461, Japan

    Takahiro Kimura & Shin Egawa

  2. Department of Urology, Kinki University, 3-4-1 Kowakae, Higashiosaka City, Osaka, 577–8502, Japan

    Hirotsugu Uemura

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T.K. researched data and wrote the article. S.E. and H.U. reviewed and/or edited the manuscript before submission.

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Correspondence to Takahiro Kimura.

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S.E. is a paid consultant/adviser to Astellas, AstraZeneca, and Takeda. H.U. is a paid consultant/adviser to AstraZeneca and Takeda. T.K. declares no competing interests.

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Kimura, T., Egawa, S. & Uemura, H. Personalized peptide vaccines and their relation to other therapies in urological cancer. Nat Rev Urol 14, 501–510 (2017). https://doi.org/10.1038/nrurol.2017.77

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