Cancer vaccines: the importance of targeting oncogenic drivers and the utility of combinations with immune checkpoint inhibitors

摘要

Evidence continues to accumulate supporting the viability of therapeutic cancer vaccines. It is now widely accepted that engagement of the adaptive immune system is a positive prognostic indicator for many types of cancer. The presence of cytotoxic T cells in tumors, engagement of CD4 T cell help, induction of tumor specific antibodies, and systemic engagement of antigen presentation and activation are all recognized as critical factors in an effective anti-tumor immune response [1, 2]. The use of a therapeutic agent like a vaccine targeting cancer antigens is an effective way to re-engage both arms of the adaptive immune response to overcome the inherent central and peripheral immune tolerance that exists against ‘self’ [3]. Ideally, vaccination will present antigens in tumor draining lymph nodes to initiate and support a durable anti-tumor response by both T cells and B cells, which can then circulate to the site of tumors to engage and destroy tumor cells. This process can further prime the immune response, as additional antigens are released from dying cancer cells and presented in secondary lymphoid organs [1]. Despite this relatively straightforward premise, the complexity of the process has led to many questions regarding the best antigen targets, vectors, timing, and combinations to optimize cancer vaccine therapeutic efficacy.