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Clinical and Developmental Immunology
Volume 2012, Article ID 586314, 14 pages
http://dx.doi.org/10.1155/2012/586314
Research Article

TCR Gene Transfer: MAGE-C2/HLA-A2 and MAGE-A3/HLA-DP4 Epitopes as Melanoma-Specific Immune Targets

1Laboratory of Experimental Tumor Immunology, Department of Medical Oncology, Erasmus MC, 3015 GE, Rotterdam, The Netherlands
2Department of Pulmonary Diseases, Erasmus MC, 3015 GE, Rotterdam, The Netherlands
3Ludwig Institute for Cancer Research Ltd, Brussels Branch, and de Duve Institute, Université Catholique de Louvain, 1200 Brussels, Belgium

Received 25 July 2011; Revised 7 October 2011; Accepted 20 October 2011

Academic Editor: Tetsuya Nakatsura

Copyright © 2012 Trudy Straetemans et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Adoptive therapy with TCR gene-engineered T cells provides an attractive and feasible treatment option for cancer patients. Further development of TCR gene therapy requires the implementation of T-cell target epitopes that prevent “on-target” reactivity towards healthy tissues and at the same time direct a clinically effective response towards tumor tissues. Candidate epitopes that meet these criteria are MAGE-C2336-344/HLA-A2 (MC2/A2) and MAGE-A3243-258/HLA-DP4 (MA3/DP4). We molecularly characterized TCRαβ genes of an MC2/A2-specific CD8 and MA3/DP4-specific CD4 T-cell clone derived from melanoma patients who responded clinically to MAGE vaccination. We identified MC2/A2 and MA3/DP4-specific TCR-Vα3/Vβ28 and TCR-Vα38/Vβ2 chains and validated these TCRs in vitro upon gene transfer into primary human T cells. The MC2 and MA3 TCR were surface-expressed and mediated CD8 T-cell functions towards melanoma cell lines and CD4 T-cell functions towards dendritic cells, respectively. We intend to start testing these MAGE-specific TCRs in phase I clinical trial.