title: Characterization of T-cell receptors directed against HLA-A*01-restricted and C*07-restricted epitopes of MAGE-A3 and MAGE-A12.
abstract: The ability of T cells that have been genetically engineered to express T-cell receptors (TCRs) directed against tumor antigens to mediate tumor regression has been demonstrated in several clinical trials. These TCRs have primarily targeted HLA-A*0201-restricted TCRs, as approximately 50% of whites, who represent the predominant population of patients who develop melanomas, expresses this HLA class I allele. These therapies could be extended to additional patients through the use of TCRs that target epitopes that are presented by additional class I alleles that are prevalent in this population such as HLA-C*07 and HLA-A*01, which are expressed by approximately 50% and 30% of the patient population respectively. Therefore, 2 TCRs that recognize an epitope of MAGE-A12 in the context of HLA-C*07 and 2 TCRs that recognize an epitope of MAGE-A3 in the context of HLA-A*01 were isolated from tumor-reactive T-cell clones and cloned in a recombinant retroviral expression vector. Comparative studies indicated that one of the 2 MAGE-A3-reactive TCRs and one of the 2 MAGE-A12-reactive TCRs were superior to the additional TCRs in conferring transduced peripheral blood mononuclear cells with the capacity to recognize a broad array of antigen and MHC-positive target cells. These results provide support for the use of these TCRs in cancer adoptive immunotherapy trials.
authors.affiliation: Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Shigui
authors.initials: S
authors.lastname: Zhu
authors.forename: Benoit J
authors.initials: BJ
authors.lastname: Van den Eynde
authors.forename: Pierre G
authors.initials: PG
authors.lastname: Coulie
authors.forename: Yong F
authors.initials: YF
authors.lastname: Li
authors.forename: Mona
authors.initials: M
authors.lastname: El-Gamil
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
authors.forename: Paul F
authors.initials: PF
authors.lastname: Robbins
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D002999:Clone Cells; D003001:Cloning, Molecular; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology*; D015236:HLA-C Antigens / Q000276:immunology*; D006801:Humans; D008545:Melanoma / Q000276:immunology / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D015236:HLA-C Antigens; C409589:MAGEA12 protein, human; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D011948:Receptors, Antigen, T-Cell