Fueling+the+engine+and+releasing+the+break：combinational+therapy+of+cancer+vaccines+and+immune+checkpoint+inhibitors.pdf

Cancer Biol Med 2015;12:201-208. doi: 10.7497/j.issn.2095-3941.2015.0046 REVIEW Fueling the engine and releasing the break: combinational therapy of cancer vaccines and immune checkpoint inhibitors 1 2 1 Jennifer Kleponis , Richard Skelton , Lei Zheng 1Department of Oncology, Department of Surgery, The Sidney Kimmel Comprehensive Cancer, The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA; 2 Masters of Health Science Program in Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21287, USA ABSTRACT Immune checkpoint inhibitors are increasingly drawing much attention in the therapeutic development for cancer treatment. However, many cancer patients do not respond to treatments with immune checkpoint inhibitors, partly because of the lack of tumor-infiltrating effector T cells. Cancer vaccines may prime patients for treatments with immune checkpoint inhibitors by inducing effector T-cell infiltration into the tumors and immune checkpoint signals. The combination of cancer vaccine and an immune checkpoint inhibitor may function synergistically to induce more effective antitumor immune responses, and clinical trials to test the combination are currently ongoing. KEYWORDS Cancer vaccine; immune checkpoint; immunotherapy; cytotoxic T-lymphocyte antigen-4 (CTLA-4); programmed death-1 (PD-1); programmed cell death ligand-1 (PD-L1) 1 Introduction