The clinical success of
monoclonal antibody immune checkpoint modulators such as
ipilimumab, which targets
cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), and the recently approved agents
nivolumab and
pembrolizumab, which target programmed cell death receptor 1 (PD-1), has stimulated renewed enthusiasm for anticancer
immunotherapy, which was heralded by Science as 'Breakthrough of the Year' in 2013. As the potential of
cancer immunotherapy has been recognized since the 1890s when William Coley showed that bacterial products could be beneficial in
cancer patients, leveraging the immune system in the treatment of
cancer is certainly not a new concept; however, earlier attempts to develop effective therapeutic
vaccines and
antibodies against solid
tumors, for example,
melanoma, frequently met with failure due in part to self-tolerance and the development of an immunosuppressive tumor microenvironment. Increased knowledge of the mechanisms through which
cancer evades the immune system and the identification of
tumor-associated
antigens (TAAs) and negative immune checkpoint regulators have led to the development of
vaccines and
monoclonal antibodies targeting specific
tumor antigens and immune checkpoints such as CTLA-4 and PD-1. This review first discusses the established targets of currently approved
cancer immunotherapies and then focuses on investigational
cancer antigens and their clinical potential. Because of the highly heterogeneous nature of
tumors, effective anticancer
immunotherapy-based treatment regimens will likely require a personalized combination of therapeutic
vaccines,
antibodies and
chemotherapy that fit the specific biology of a patient's disease.