title: Targeting neoantigens for cancer immunotherapy.
abstract: Studies first carried out in the 1980s have demonstrated murine T cells can recognize mutated gene products, known as neoantigens, and that these T cells are capable of mediating tumor rejection. The first human tumor antigens isolated in the early 1990s were the products of non-mutated genes expressed in a tissue-specific manner; subsequent studies have indicated that tumor-infiltrating lymphocytes that are cultured in vitro frequently recognize mutated gene products. In addition, correlative studies indicate that clinical responses to therapies involving the use of antibodies directed against checkpoint inhibitors such as CTLA-4 and PD-1 may be associated with mutational burden, providing indirect evidence that these responses may primarily be mediated by neoantigen-reactive T cells. The importance of neoantigen-reactive T cells may be elucidated by the results of ongoing and future studies aimed at leveraging information gained from mutational profiling to enhance the potency of immunotherapies.
authors.affiliation: Surgery Branch, National Cancer Institute, National Institutes of Health, Building 10-CRC, Rm 3W-5744, 10 Center Drive, Bethesda, MD 20892, USA.
authors.forename: Yong-Chen
authors.initials: YC
authors.lastname: Lu
authors.affiliation: Surgery Branch, National Cancer Institute, National Institutes of Health, Building 10-CRC, Rm 3W-5744, 10 Center Drive, Bethesda, MD 20892, USA paul_robbins@nih.gov.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Robbins
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology; D060908:CTLA-4 Antigen / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D060908:CTLA-4 Antigen; D019496:Cancer Vaccines; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: cancer immunotherapy; mutation; neoantigen; tumor immunology