More T cell receptors to the RAScue in cancer?

J Clin Invest. 2024 Nov 1;134(21):e184782. doi: 10.1172/JCI184782.

Abstract

Treatment with T cells genetically engineered to express tumor-reactive T cell receptors (TCRs), known as TCR-gene therapy (TCR-T), is a promising immunotherapeutic approach for patients with cancer. The identification of optimal TCRs to use and tumor antigens to target are key considerations for TCR-T. In this issue of the JCI, Bear and colleagues report on their use of in vitro assays to characterize four HLA-A*03:01- or HLA-A*11:01-restricted TCRs targeting the oncogenic KRAS G12V mutation. The TCRs were derived from healthy donors or patients with pancreatic cancer who had received a vaccine against mutant KRAS. The most promising TCRs warrant testing in patients with KRAS G12V-positive cancers.

MeSH terms

  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology
  • Cancer Vaccines / immunology
  • HLA-A Antigens / genetics
  • HLA-A Antigens / immunology
  • HLA-A Antigens / metabolism
  • Humans
  • Mutation
  • Mutation, Missense
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / therapy
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / therapy
  • Proto-Oncogene Proteins p21(ras)* / genetics
  • Proto-Oncogene Proteins p21(ras)* / immunology
  • Proto-Oncogene Proteins p21(ras)* / metabolism
  • Receptors, Antigen, T-Cell* / genetics
  • Receptors, Antigen, T-Cell* / immunology
  • Receptors, Antigen, T-Cell* / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Receptors, Antigen, T-Cell
  • Proto-Oncogene Proteins p21(ras)
  • KRAS protein, human
  • Antigens, Neoplasm
  • HLA-A Antigens
  • Cancer Vaccines