TGF‐β–responsive CAR‐T cells promote anti‐tumor immune function

Bioengineering and Translational Medicine - Tập 3 Số 2 - Trang 75-86 - 2018
Andrew J. Hou1,2, ZeNan Chang1,3,2, Michael H. Lorenzini4, Eugenia Zah1, Yvonne Y. Chen1,5
1Dept. of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA 90095
2These authors contributed equally
3Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA 90095
4Dept. of Bioengineering, University of California Los Angeles, Los Angeles, CA, 90095
5Parker Institute for Cancer Immunotherapy Center at UCLA, Los Angeles, CA 90095

Tóm tắt

AbstractA chimeric antigen receptor (CAR) that responds to transforming growth factor beta (TGF‐β) enables the engineering of T cells that convert this immunosuppressive cytokine into a potent T‐cell stimulant. However, clinical translation of TGF‐β CAR‐T cells for cancer therapy requires the ability to productively combine TGF‐β responsiveness with tumor‐targeting specificity. Furthermore, the potential concern that contaminating, TGF‐β?producing regulatory T (Treg) cells may preferentially expand during TGF‐β CAR‐T cell manufacturing and suppress effector T (Teff) cells demands careful evaluation. Here, we demonstrate that TGF‐β CAR‐T cells significantly improve the anti‐tumor efficacy of neighboring cytotoxic T cells. Furthermore, the introduction of TGF‐β CARs into mixed T‐cell populations does not result in the preferential expansion of Treg cells, nor do TGF‐β CAR‐Treg cells cause CAR‐mediated suppression of Teff cells. These results support the utility of incorporating TGF‐β CARs in the development of adoptive T‐cell therapy for cancer.

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Tài liệu tham khảo

Press Announcements – FDA approves CAR‐T cell therapy to treat adults with certain types of large B‐cell lymphoma.https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm581216.htm. Accessed February 6 2018.

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Bioengineering and Translational Medicine

Tập 3 Số 2

75-86

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