The role of active vaccination in cancer immunotherapy: lessons from clinical trials

•Vaccine clinical trials suggests a variable immune and clinical response to vaccines.•Immune exhaustion is a crucial problem limiting maximum vaccine response.•Combining vaccines and co-targeting CD8 exhaustion may give a better vaccine response.

In the past few years, a number of different immunotherapeutic strategies have shown impressive results in cancer patients. These successful approaches include blockade of immunosuppressive molecules like PD-1 and CTLA-4, adoptive transfer of patient derived and genetically modified T-cells, and vaccines that stimulate tumor antigen specific T-cells. However, several large vaccine trials recently failed to reach designated primary endpoints. In light of the success of other immunotherapeutic approaches, these negative results raise the questions of why vaccines have not generated a better response, and what the role of active vaccination will be moving forward in cancer immunotherapy.