Neoantigen vaccine platforms in clinical development: understanding the future of personalized immunotherapy

ABSTRACT

Introduction

Derived from genetic alterations, cancer neoantigens are proteins with novel amino acid sequences that can be recognized by the immune system. Recent evidence demonstrates that cancer neoantigens represent important targets of cancer immunotherapy. The goal of cancer neoantigen vaccines is to induce neoantigen-specific immune responses and antitumor immunity, while minimizing the potential for autoimmune toxicity. Advances in sequencing technologies, neoantigen prediction ?algorithms,? and other technologies have dramatically improved the ability to identify and prioritize cancer neoantigens. These advances have generated considerable enthusiasm for ?the ?development of neoantigen vaccines. Several neoantigen vaccine platforms are currently being evaluated in early phase clinical trials including the synthetic long peptide (SLP), RNA, dendritic cell (DC), and DNA vaccine platforms.

Areas covered

In this review, we describe, evaluate the mechanism(s) of action, compare the advantages and disadvantages, and summarize early clinical experience with each vaccine platform. We provide perspectives on the future directions of the neoantigen vaccine field. All data are derived from PubMed and ClinicalTrials search updated in October 2020.

Expert opinion

Although the initial clinical experience is promising, significant challenges to the success of neoantigen vaccines include limitations in neoantigen identification and the need to successfully target the immunosuppressive tumor microenvironment.

KEYWORDS:

• Neoantigen
• cancer vaccine
• delivery platforms
• clinical trial

ARTICLE HIGHLIGHTS

• The goal of cancer neoantigen vaccines is to induce neoantigen-specific immune responses and antitumor immunity, while minimizing the potential for autoimmune toxicity.

• For a successful neoantigen cancer vaccine, neoantigen identification, prioritization, and delivery platform are important components in a vaccine manufacturing workflow.

• Several neoantigen vaccine platforms are currently being evaluated in early phase clinical trials including the synthetic long peptide (SLP), RNA, dendritic cell (DC), and DNA vaccine platforms, and it remains unclear if one platform is superior.

• Although each vaccine platform has different formulations, routes of administration, and mechanism(s) of action, they share a common goal of presentation of cancer neoantigens to T cells in the context of appropriate stimulatory signals.

• The success of neoantigen vaccines may depend on combination with other cancer immunotherapies such as immune checkpoint inhibition, and/or immune modulatory agents targeting the tumor microenvironment.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no other 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 apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This project was supported by grants from Susan G. Komen for the Cure (KG111025), the Alvin J. Siteman Cancer Center (Siteman Investment Program grant 4035), The National Institute of Health (NIH) Research Project Grant R01 CA240983, the National Cancer Institute at the NIH (Cancer Center Support Grant P30-CA091842 and SPORE in Pancreatic Cancer P50-CA196510), the Foundation for Barnes-Jewish Hospital (to SPG), and Prince Mahidol Award Youth Program of Prince Mahidol Award Foundation under the Royal Patronage of HM the king of Thailand (to SS).