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Enhancing the efficacy of cancer vaccines in urologic oncology: new directions

Nature Reviews Urology volume 6, pages 540–549 (2009)Cite this article

Abstract

Immunotherapeutic interventions have long been utilized in urologic oncology for the treatment of metastatic renal cell or superficial transitional cell carcinoma. Most recently, the first active specific immunotherapeutic approach, a cancer vaccine, has passed the final phase of human testing and its approval by the FDA is pending. However, evidence suggests that the full protective and therapeutic potential of cancer vaccines has not yet been achieved. Through multiple mechanisms, tumors promote conditions in the tumor-bearing host that mitigate or even eliminate the vaccine-induced antitumor response. Restoration of the impaired immune function is, therefore, imperative for achieving optimum vaccine efficacy. Targeted pharmacological interventions are capable of overcoming tumor-mediated immunosuppression, and thereby enable cancer vaccination to reach its full therapeutic potential.

Key Points

  • Cancer vaccines are designed to stimulate an antitumor immune response via expansion of the cellular arm of the immune system, especially T cells or natural killer cells

  • At present, the therapeutic effect of cancer vaccines in patients with advanced genitourinary cancers is limited

  • In patients with cancer, tumors promote immunosuppression via multiple mechanisms including secretion of tumor-derived factors, mobilization of bone-marrow-derived suppressor myeloid cells and induction of T-regulatory cells

  • An immunosuppressive microenvironment helps cancer cells to evade immune recognition and immune-mediated destruction

  • Simultaneous targeting of tumor-induced immune suppression and administration of a cancer vaccine has great potential to boost the antitumor immune response and produce a more-powerful therapeutic effect than vaccination alone

  • Clinical trials that are investigating combinatorial approaches that entail abrogation of tumor-induced immunosuppression followed by active immunotherapy are ongoing in many academic and industry programs

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Figure 1: The T-cell response against cancer.
Figure 2: Elevated numbers of immunosuppressive myeloid cells in the peripheral blood of patients with cancer.
Figure 3: Tumor-infiltrated myeloid cells contribute to the immunosuppressive network in tumors.

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  1. Department of Urology, Prostate Disease Center, University of Florida College of Medicine, Gainesville, FL, USA

    Sergei Kusmartsev & Johannes Vieweg

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J. Vieweg declares that he has acted as a member of the Advisory Council for CureVac. S. Kusmartsev declares no competing interests.

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Kusmartsev, S., Vieweg, J. Enhancing the efficacy of cancer vaccines in urologic oncology: new directions. Nat Rev Urol 6, 540–549 (2009). https://doi.org/10.1038/nrurol.2009.177

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