TRICOM poxviral-based vaccines for the treatment of cancer

Abstract

TRICOM poxviral-based vaccines are novel off-the-shelf agents designed to generate a robust immune response against tumor-associated antigens, which are commonly expressed on tumor cells. In this chapter, we elucidate the science behind the development and use of these vaccines. We also highlight the results of preclinical and clinical trials of these vaccines and the potential benefits of combining them with standard-of-care chemotherapy and other immunotherapies. We compare the immune-stimulating effects of replication-competent versus replication-defective poxviral vectors and the rationale for using a diversified prime-boost regimen. We review current knowledge of tumor-associated antigens, including agonist epitopes and antigen spreading (or antigen cascade), as well as the use of immunostimulatory agents and T-cell costimulatory molecules. We also provide descriptions of completed and ongoing clinical trials of various TRICOM poxviral-based vaccines, including safety studies, phase II trials with vaccine alone, vaccine plus standard-of-care regimens, and an ongoing multicenter phase III trial. We discuss tumor growth kinetics, an important emerging predictive factor for survival, in the context of immunotherapy for prostate cancer and, finally, propose potential strategies for maximizing the clinical impact of TRICOM poxviral-based vaccines.