Neoadjuvant personalized cancer vaccines: the final frontier?

ABSTRACT

Introduction

Clinical trials of personalized cancer vaccines have shown that on-demand therapies that are manufactured for each patient, result in activated T cell responses against individual tumor neoantigens. However, their use has been traditionally restricted to adjuvant settings and late-stage cancer therapy. There is growing support for the implementation of PCV earlier in the cancer therapy timeline, for reasons that will be discussed in this review.

Areas covered

The efficacy of cancer vaccines may be to some extent dependent on treatment(s) given prior to vaccine administration. Tumors can undergo radical immunoediting following treatment with immunotherapies, such as checkpoint inhibitors, which may affect the presence of the very mutations targeted by cancer vaccines. This review will cover the topics of neoantigen cancer vaccines, tumor immunoediting, and therapy timing.

Expert opinion

Therapy timing remains a critical topic to address in optimizing the efficacy of personalized cancer vaccines. Most personalized cancer vaccines are being evaluated in late-stage cancer patients and after treatment with checkpoint inhibitors, but they may offer a greater benefit to the patient if administered in earlier clinical settings, such as the neoadjuvant setting, where patients are not facing T cell exhaustion and/or a further compromised immune system.

KEYWORDS:

• Checkpoint inhibitor
• immunoinformatics
• immunotherapy
• personalized cancer vaccine
• neoadjuvant therapy
• neoantigen
• T cell
• therapy timing

Article highlights

• Personalized cancer vaccines have regained interest given recent positive clinical trial results.

• Personalized cancer vaccines are currently being evaluated in the adjuvant setting and after treatment with checkpoint inhibitors.

• Tumors may radically undergo immunoediting after treatment with checkpoint inhibitors, affecting the presence of mutations targeted by cancer vaccines.

• Personalized cancer vaccines may be most effective in earlier clinical settings before surgery and checkpoint inhibitor therapy.

Declaration of interest

A De Groot and WD Martin are senior officers and majority shareholders of EpiVax, Inc, a privately owned immunoinformatics and vaccine design company. G Richard is a senior officer, N Ruggiero was a senior officer of EpiVax Therapeutics, Inc., a precision immunotherapy company and subsidiary of EpiVax, Inc. G Richard and N Ruggiero have equity in EpiVax Therapeutics. GD Steinberg is a member of Clinical Trial Protocol Committees for the following companies: Merck, BMS, Janssen, Cold Genesys, Pfizer, PhotoCure, Fidia, is or has been a scientific advisor/consultant within the past 5 years for the following companies: Heat Biologics, Cold Genesys, PhotoCure, Merck, Roche/Genentech, Ciclomed, Taris Biomedical, MDxHealth, Fidia Farmaceuticals, Urogen, Ferring, Aduro, Boston Scientific, Bristol Myers Squibb, Astra Zeneca, Pfizer, Janssen, EpiVax Therapeutics, Natera, FKD, Ferring, EnGene Bio, SesenBio, BioCanCell, Nucleix, Ipsen, Combat Medical, Astellas, Fergene, Dendreon, Abbvie, Seattle Genetics, and has equity stock/options in EpiVax Therapeutics and Urogen. 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

Reviewers on this manuscript have received honorarium for their review work. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Author contributions

G Richard and A De Groot drafted the manuscript. All authors made substantial edits, reviewed, and approved the manuscript for submission.

Additional information

Funding

This paper was not funded.