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

Shigui Zhu, Benoit J. Van Den Eynde, Pierre G. Coulie, Yong F. Li, Mona El-Gamil, Steven A. Rosenberg, Paul F. Robbins

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)680-688
Number of pages9
JournalJournal of Immunotherapy
Volume35
Issue number9
DOIs
StatePublished - Nov 2012

Keywords

  • T-cell epitopes
  • T-cell receptors
  • cancer immunotherapy
  • cancer/germline antigens

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

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