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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.

Original publication

DOI

10.1097/CJI.0b013e31827338ea

Type

Journal article

Journal

J Immunother

Publication Date

11/2012

Volume

35

Pages

680 - 688

Keywords

Antigens, Neoplasm, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Line, Tumor, Clone Cells, Cloning, Molecular, Cytotoxicity, Immunologic, Epitopes, T-Lymphocyte, HLA-A Antigens, HLA-C Antigens, Humans, Melanoma, Neoplasm Proteins, Receptors, Antigen, T-Cell, T-Lymphocytes, Transduction, Genetic