The future of cancer vaccines against colorectal cancer

ABSTRACT

Introduction

Colorectal cancer (CRC) is the second most lethal malignancy worldwide. Immune checkpoint inhibitors (ICIs) benefit only 15% of patients with mismatch repair-deficient/microsatellite instability (dMMR/MSI) CRC. The majority of patients are not suitable due to insufficient immune infiltration. Cancer vaccines are a potential approach for inducing tumor-specific immunity within the solid tumor microenvironment.

Area covered

In this review, we have provided an overview of the current progress in CRC vaccines over the past three years and briefly depict promising directions for further exploration.

Expert opinion

Cancer vaccines are certainly a promising field for the antitumor treatment against CRC. Compared to monotherapy, cancer vaccines are more appropriate as adjuvants to standard treatment, especially in combination with ICI blockade, for microsatellite stable patients. Improved vaccine construction requires neoantigens with sufficient immunogenicity, satisfactory HLA-binding affinity, and an ideal delivery platform with perfect lymph node retention and minimal off-target effects. Prophylactic vaccines that potentially prevent CRC carcinogenesis are also worth investigating. The exploration of appropriate biomarkers for cancer vaccines may benefit prognostic prediction analysis and therapeutic response prediction in patients with CRC. Although many challenges remain, CRC vaccines represent an exciting area of research that may become an effective addition to current guidelines.

KEYWORDS:

• Colorectal cancer
• vaccine
• neoantigen
• dendritic cell vaccine
• nanovaccine
• immunotherapy

Article highlights

• Cancer vaccines represent a promising category of potential treatments for microsatellite stable patients.

• Different types of CRC vaccines have been widely tested in preclinical and phase I/II clinical trials.

• Adjuvants and route of administration are crucial points to be considered.

• Recent developments and promising directions for further exploration fall into five different aspects, including combined therapy, screening for neoantigens, nanovaccines, vaccines against oncomicrobes that lead to CRC, and prophylactic vaccines for high-risk populations.

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.

Reviewer disclosures

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

Acknowledgments

Language editing has been provided by Editage.com.

Additional information

Funding

This paper was funded by the National Natural Science Foundation of China (Grant 82271766; to R Zhao), the National Natural Science Foundation of China (Grant 82002475; to X Cheng) and the Shanghai “Rising Stars of Medical Talents” Youth Development Program (Youth Medical Talents - Specialist Program; to X Cheng).