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Inventi Impact: Gene Medicines

Articles

  • Inventi:pgm/54/12
    TCR GENE TRANSFER: MAGE-C2/HLA-A2 AND MAGE-A3/HLA-DP4 EPITOPES AS MELANOMA-SPECIFIC IMMUNE TARGETS
    30-Sep-2012 Research 2012 : October - December
    Trudy Straetemans, Mandy van Brakel, Sabine van Steenbergen, Marieke Broertjes, Joost Drexhage, Joost Hegmans, Bart N Lambrecht, Cor Lamers, Pierre van Der Bruggen, Pierre G Coulie, Reno Debets

    Adoptive therapy with TCR gene-engineered T cells provides an attractive and feasible treatment option for cancer patients.\r\nFurther development of TCR gene therapy requires the implementation of T-cell target epitopes that prevent ââ?¬Å?on-targetââ?¬Â reactivity\r\ntowards healthy tissues and at the same time direct a clinically effective response towards tumor tissues. Candidate epitopes\r\nthat meet these criteria are MAGE-C2336-344/HLA-A2 (MC2/A2) and MAGE-A3243-258/HLA-DP4 (MA3/DP4). We molecularly\r\ncharacterized TCRaÃ?Ÿ genes of an MC2/A2-specific CD8 and MA3/DP4-specific CD4 T-cell clone derived from melanoma\r\npatients who responded clinically to MAGE vaccination.We identified MC2/A2 and MA3/DP4-specific TCR-Va3/VÃ?Ÿ28 and TCRVa38/\r\nVÃ?Ÿ2 chains and validated these TCRs in vitro upon gene transfer into primary human T cells. The MC2 and MA3 TCR were\r\nsurface-expressed and mediated CD8 T-cell functions towards melanoma cell lines and CD4 T-cell functions towards dendritic\r\ncells, respectively.We intend to start testing these MAGE-specific TCRs in phase I clinical trial.

    How to Cite this Article
    CC Compliant Citation: Trudy Straetemans, Mandy van Brakel,\r\nSabine van Steenbergen, et al., â??TCR Gene Transfer: MAGE-C2/\r\nHLA-A2 and MAGE-A3/HLA-DP4 Epitopes as Melanoma-Specific\r\nImmune Targets,â? Clinical and Developmental Immunology, vol.\r\n2012, Article ID 586314, 14 pages, 2012.\r\ndoi:10.1155/2012/586314.
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