Characterization of T cell receptors directed against HLA-A*01 and C*07 restricted epitopes of MAGE-A3 and MAGE-A12

摘要

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 Caucasians, 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 patients, respectively. Therefore, two TCRs that recognize an epitope of MAGE-A12 in the context of HLA-C*07, as well as two 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 two MAGE-A3 reactive TCRs and one of the two MAGE-A12 reactive TCRs were superior to the additional TCRs in conferring transduced PBMC with the capacity to recognize a broad array of antigen and MHC positive target cells. These results provide support the use of these TCRs in cancer adoptive immunotherapy trials.