TCR Gene Transfer: MAGE-C2/HLA-A2 and MAGE-A3/HLA-DP4 Epitopes as Melanoma-Specific Immune Targets. (12th February 2012)

• Record Type: Journal Article
• Authors: Straetemans, Trudy; van Brakel, Mandy; van Steenbergen, Sabine; Broertjes, Marieke; Drexhage, Joost; Hegmans, Joost; Lambrecht, Bart N.; Lamers, Cor; Bruggen, Pierre van Der; Coulie, Pierre G.; Debets, Reno
• Other Names: Nakatsura Tetsuya Academic Editor.
• Is Part Of: Clinical & developmental immunology. Volume 2012(2012)
• Publication Date: 2012-02-12
• Subjects: Developmental immunology -- Periodicals; Clinical immunology -- Periodicals; Immune System -- immunology -- Periodicals; Immune System -- growth & development -- Periodicals; Immune System Diseases -- immunology -- Periodicals; 571.9638
• DOI: 10.1155/2012/586314
• Languages: English
• ISSNs: 1740-2522

Abstract

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 TCR αβ 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-V α 3/V β 28 and TCR-V α 38/V β 2 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.