Considerations for the combination of anticancer vaccines and immune checkpoint inhibitors.

INTRODUCTION: Over the past few years, trials evaluating immunotherapies, particularly immune checkpoint inhibitors, have revolutionized the standard model of cancer treatment, demonstrating significant antitumor responses and improved clinical outcomes across a wide array of tumors types. Yet, despite these compelling data, a major limitation has been that only a fraction of patients mount a response to single-agent immune checkpoint inhibition. However, a growing amount of preclinical and clinical data suggests that combining immune checkpoint inhibition, either with other immune checkpoint inhibitors or with therapeutic cancer vaccines, has the potential to improve the proportion of patients seeing long-term durable responses with these therapies. AREAS COVERED: We have reviewed the reported data on immune checkpoint inhibition as monotherapy and as combination therapy with other immune checkpoint inhibitors or therapeutic cancer vaccines. Data is reviewed on agents with FDA approval or breakthrough designation as of the writing of this manuscript. EXPERT OPINION: Particular focus is given to the combination of immune checkpoint inhibitors and therapeutic cancer vaccines which has the potential to increase efficacy compared to single agent immune checkpoint inhibition with minimal added toxicity.

Adding fuel to the fire: immunogenic intensification.

The durable long term clinical benefits seen for certain patients treated with immunotherapy agents has suggested there is significant therapeutic potential to be derived from these agents, as shown by the increasing prominence of this treatment strategy in upcoming clinical trials. There has been a renewed interest and focus on the drivers of tumoral antigen recognition, and the pathways by which various cells of the immune system can stimulate, propagate and execute an effective anti-tumor response. Various challenges lie ahead in the further development of these treatments, including induction of an endogenous anti-tumor response, tumor microenvironment modulation, and T-cell response amplification. Novel treatment combinations may prove of significant added benefit by immunogenic intensification.