Spectrum of Current Therapeutic Cancer Vaccine Platforms

This article reviews the current state of the design, development, and clinical applications of therapeutic cancer vaccines. The numerous previous failures of cancer vaccines may be attributed to the fact that not all vaccines are created equal (there has been a clear evolution in vaccine design) and/or to issues in clinical trial design and patient population. This article covers the diversity of therapeutic cancer vaccine platforms and the wide range of tumorassociated antigens being targeted; the current state of clinical trials that test therapeutic cancer vaccines, including the results of recent randomized multicenter phase II and phase III studies; issues to be considered in future clinical trials; the profound influence of the tumor microenvironment and immunosuppressive factors in inhibiting optimal vaccine efficacy and potential strategies to combat these phenomena; combinatorial therapies, including the use of cancer vaccines with immune stimulants, inhibitors of immune suppression, certain chemotherapeutic agents, smallmolecule targeted therapies, hormones, and radiation; the potential use of biomarkers to select those patients who are most likely to benefit from vaccine therapy; and other future directions in this field. This article is not designed to comprehensively review all preclinical and clinical studies of therapeutic cancer vaccine, but instead, to delineate the factors and concepts that are currently being evaluated to develop vaccines as therapeutics for a wide range of human cancers and cancer stages, either as monotherapies or as combination therapies.