Considerations for the combination of anticancer vaccines and immune checkpoint inhibitors

ABSTRACT

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.

KEYWORDS:

• Immune checkpoint inhibitors
• therapeutic cancer vaccines
• immunogenic intensification

Article highlights

• In recent years, monoclonal antibodies against PD-1 and its ligand (PD-L1) have demonstrated impressive clinical efficacy in multiple tumors.

• Data suggest that mismatch repair deficiency may predispose to response from immune checkpoint inhibition by creating a high somatic mutational and antigenic burden in tumors.

• Data suggest that responses to PD-1/PD-L1 blockade may correlate with PD-L1 expression in the TME.

• Emerging data suggest that a number of immunotherapy agents have the potential to drive activated T lymphocytes into the tumor, resulting in PD-L1 upregulation. This combined immune stimulation using multiple immunotherapies could theoretically increase the number of patients who respond to immune checkpoint inhibition.

• The combination of immune checkpoint inhibitors and therapeutic cancer vaccines is of particular interest as it has the potential to increase efficacy compared to single agent immune checkpoint inhibition with minimal added toxicity.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.