Identification of Antigenic Targets

Trends Cancer. 2020 Apr;6(4):299-318. doi: 10.1016/j.trecan.2020.01.002. Epub 2020 Feb 20.

Abstract

The ideal cancer target antigen (Ag) is expressed at high copy numbers on neoplastic cells, absent on normal tissues, and contributes to the survival of cancer cells. Despite significant investments in the identification of cell surface Ags, there is a paucity of targets that meet such ideal cancer target criteria. Recent clinical trials in patients with cancer treated with immune checkpoint inhibitors (ICIs) indicate that cluster of differentiation (CD)8+ T cells, by means of their T cell receptors (TCRs) recognizing intracellular targets presented as peptides in the context of human leukocyte antigen (peptide-human leukocyte antigen complex; pHLA) molecules on tumor cells, can mediate deep and long-lasting antitumor responses in patients with solid tumors. Therefore, pHLA-target Ags may represent the long sought-after, ideal targets for solid tumor targeting by high-potency oncology compounds.

Keywords: T cell receptor; adoptive T cell therapy; intracellular targets; pHLA complex.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / metabolism*
  • Antineoplastic Agents, Immunological / pharmacology*
  • Antineoplastic Agents, Immunological / therapeutic use
  • Cell Line, Tumor
  • Computer Simulation
  • Cross Reactions / immunology
  • Drug Discovery / methods*
  • Epitope Mapping / methods
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / immunology
  • HLA Antigens / genetics
  • HLA Antigens / immunology
  • HLA Antigens / metabolism
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immune Checkpoint Inhibitors / therapeutic use
  • Ligands
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Peptide Library
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Antigens, Neoplasm
  • Antineoplastic Agents, Immunological
  • Epitopes, T-Lymphocyte
  • HLA Antigens
  • Immune Checkpoint Inhibitors
  • Ligands
  • Peptide Library
  • Receptors, Antigen, T-Cell