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Isolation and Characterization of an HLA-DPB1*04: 01-restricted MAGE-A3 T-Cell Receptor for Cancer Immunotherapy

Yao, Xin et al.

Journal of immunotherapy: official journal of the Society for Biological Therapy. Volume 39:Issue 5 (2016, June) -- Lippincott Williams & Wilkins

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  • Title:
    Isolation and Characterization of an HLA-DPB1*04: 01-restricted MAGE-A3 T-Cell Receptor for Cancer Immunotherapy
  • Author: Yao, Xin;
    Lu, Yong-Chen;
    Parker, Linda L.;
    Li, Yong F.;
    El-Gamil, Mona;
    Black, Mary A.;
    Xu, Hui;
    Feldman, Steven A.;
    van der Bruggen, Pierre;
    Rosenberg, Steven A.;
    Robbins, Paul F.
  • Found In: Journal of immunotherapy: official journal of the Society for Biological Therapy. Volume 39:Issue 5 (2016, June)
  • Journal Title: Journal of immunotherapy: official journal of the Society for Biological Therapy
  • Subjects: Neoplasms--therapy--Periodicals; Electronic journals; Immunotherapy--Periodicals; cancer-germline antigens--cancer immunotherapy--tumor immunology; Dewey: 615.37
  • Rights: legaldeposit
  • Publication Details: Lippincott Williams & Wilkins
  • Abstract: Abstract :

    Long-term tumor regressions have been observed in patients following the adoptive transfer of autologous tumor-infiltrating lymphocytes or genetically modified T cells expressing MHC class I-restricted T-cell receptors (TCRs), but clinical trials have not evaluated responses to genetically modified T cells expressing antitumor MHC class II-restricted TCRs. As studies carried out in a murine tumor model system have demonstrated that the adoptive transfer of CD4 + T cells could lead to the regression of established tumors, we plan to test the hypothesis that CD4 + T cells can also induce tumor regressions in cancer patients. In this study, 2 MAGE-A3-specific TCRs were isolated from a regulatory T-cell clone (6F9) and an effector clone (R12C9), generated from the peripheral blood of 2 melanoma patients after MAGE-A3 vaccination. The results indicated that T cells transduced with 6F9 TCR mediated stronger effector functions than R12C9 TCR. The 6F9 TCR specifically recognized MAGE-A3 and the closely related MAGE-A6 gene product, but not other members of the MAGE-A family in the context of HLA-DPB1*04:01. To test the feasibility of a potential clinical trial using this TCR, a clinical-scale procedure was developed to obtain a large number of purified CD4 + T cells transduced with 6F9 TCR. Because HLA-DPB1*04:01 is present in ∼60% of the Caucasian population and MAGE-A3 is frequently expressed in a variety of cancer types, this TCR immunotherapy could potentially be applicable for a significant portion of cancer patients.

    Abstract :

    Supplemental Digital Content is available in the text.


  • Identifier: System Number: LDEAvdc_100049237831.0x000001; Journal ISSN: 1524-9557; 10.1097/CJI.0000000000000123
  • Publication Date: 2016
  • Physical Description: Electronic
  • Shelfmark(s): ELD Digital store

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