TCR affinity for p/MHC formed by tumor antigens that are self-proteins: impact on efficacy and toxicity

Curr Opin Immunol. 2015 Apr;33:16-22. doi: 10.1016/j.coi.2015.01.003. Epub 2015 Jan 22.

Abstract

Recent studies have shown that the range of affinities of T cell receptors (TCRs) against non-mutated cancer peptide/class I complexes are lower than TCR affinities for foreign antigens. Raising the affinity of TCRs for optimal activity of CD8 T cells, and for recruitment of CD4 T cell activity against a class I antigen, provides opportunities for more robust adoptive T cell therapies. However, TCRs with enhanced affinities also risk increased reactivity with structurally related self-peptides, and off-target toxicities. Careful selection of tumor peptide antigens, in silico proteome screens, and in vitro peptide specificity assays will be important in the development of the most effective, safe TCR-based adoptive therapies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antigens, Neoplasm / chemistry
  • Antigens, Neoplasm / immunology*
  • Antigens, Neoplasm / metabolism*
  • Cross Reactions / immunology
  • Epitopes, T-Lymphocyte / immunology
  • Epitopes, T-Lymphocyte / metabolism
  • Histocompatibility Antigens / chemistry
  • Histocompatibility Antigens / immunology*
  • Histocompatibility Antigens / metabolism*
  • Humans
  • Immunotherapy, Adoptive / adverse effects
  • Immunotherapy, Adoptive / methods
  • Lymphocyte Activation / immunology
  • Neoplasms / immunology*
  • Neoplasms / metabolism*
  • Neoplasms / therapy
  • Protein Binding
  • Receptors, Antigen, T-Cell / chemistry
  • Receptors, Antigen, T-Cell / metabolism*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism

Substances

  • Antigens, Neoplasm
  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens
  • Receptors, Antigen, T-Cell