Cancer vaccines: Targeting KRAS-driven cancers

Expert Rev Vaccines. 2020 Feb;19(2):163-173. doi: 10.1080/14760584.2020.1733420. Epub 2020 Mar 14.

Abstract

Introduction: Mutant KRAS is a genetic driver of multiple cancers that has challenged clinical anti-cancer therapeutics in the last 3 decades. Neo-antigens encoded by KRAS mutations have been identified as tumor-specific with high immunogenicity and can be used to deliver precision cancer vaccines to promote anti-tumor immune responses. KRAS mutation-based cancer vaccines have produced encouraging preclinical and clinical results. Cancer vaccines represent a promising approach to treat KRAS-driven cancers.Areas covered: In this review, we summarize the development and progress of vaccines targeting KRAS and evaluate their potential benefits and obstacles in the current landscape of therapy for KRAS-driven cancers.Expert opinion: KRAS mutation-based cancer vaccines can induce immunogenicity in patients with KRAS-driven cancers. However, the mechanisms of tumor suppression including cellular and molecular factors within the tumor microenvironment may limit vaccine efficacy. Combining KRAS-driven therapeutic cancer vaccines with other methods and adjuvants can circumvent immunosuppression and promote therapeutic successes.

Keywords: KRAS mutation; colorectal cancer; lung cancer; neo-antigen vaccine; pancreatic cancer; peptide vaccine.

Publication types

  • Review

MeSH terms

  • Animals
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / immunology
  • Humans
  • Immunogenicity, Vaccine
  • Mutation
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / prevention & control*
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Tumor Microenvironment

Substances

  • Cancer Vaccines
  • KRAS protein, human
  • Proto-Oncogene Proteins p21(ras)