Isolation and Characterization of an HLA-DPB1*04
(2016) Journal of Immunotherapy — Vol. 39, n° 5, p. 191-201 (2016)
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- 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.
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Yao, X., Lu, Y.-C., Parker, L. L., Li, Y. F., El-Gamil, M., Black, M. A., Xu, H., Feldman, S. A., van der Bruggen, P., Rosenberg, S. A., & Robbins, P. F. (2016). Isolation and Characterization of an HLA-DPB1*04. Journal of Immunotherapy, 39(5), 191-201. https://doi.org/10.1097/CJI.0000000000000123 (Original work published 2016)