Getting personal in metastatic melanoma: neoantigen-based vaccines as a new therapeutic strategy

Abstract

Purpose of review: Cancer vaccines are facing renewed interest, thanks to the progress recently achieved in the immunotherapy field, including the success of immune checkpoint inhibitors (CPIs). The advances in understanding the CPI mode of action revealed a central role of neoantigens for the outcome of such treatments. Neoantigens became the preferred antigens for cancer vaccines and have been evaluated in several clinical trials. Here, we review the recent results from neoantigen-based vaccines in melanoma patients and discuss avenues for improvement.

Recent findings: The importance of neoantigens for tumor control comes from the positive correlation between tumor mutational burden (TMB) and response to CPI. Preclinical studies have proved the effectiveness of neoantigen vaccines in models, expediting their clinical testing. Tumor mutations are not shared in most tumor types including melanoma, mandating the need of a personalized approach. Several clinical studies have shown the safety, feasibility, immunogenicity and preliminary evidence of antitumor activity of personalized vaccination. Currently, new trials have been started aiming to both confirm clinical activity and combining vaccines with other immunotherapies for improved efficacy.

Summary: Personalized vaccines hold the promise for highly mutated and immunogenic cancers, including melanoma. Continuous efforts are underway to increase their likelihood of success.

Box 1

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FIGURE 1

Overview of the process for generation of personalized neoantigen-based cancer vaccine. The first step for developing neoantigen cancer vaccine is the identification of mutated tumor-specific antigens from the patient tumor biopsy by whole exome/transcriptome sequencing and prediction of immunogenic MHC epitopes. Next, vaccines (e.g. viral vectors, mRNA, peptides) are manufactured and aministered in patients.