CXCR5 CAR-T cells simultaneously target B cell non-Hodgkin's lymphoma and tumor-supportive follicular T helper cells.

Autor:	Bunse M; Max-Delbrück-Center for Molecular Medicine, MDC, Department of Microenvironmental Regulation in Autoimmunity and Cancer, 13125, Berlin, Germany., Pfeilschifter J; Max-Delbrück-Center for Molecular Medicine, MDC, Department of Microenvironmental Regulation in Autoimmunity and Cancer, 13125, Berlin, Germany., Bluhm J; Max-Delbrück-Center for Molecular Medicine, MDC, Department of Translational Tumorimmunology, 13125, Berlin, Germany., Zschummel M; Max-Delbrück-Center for Molecular Medicine, MDC, Department of Microenvironmental Regulation in Autoimmunity and Cancer, 13125, Berlin, Germany., Joedicke JJ; Max-Delbrück-Center for Molecular Medicine, MDC, Department of Microenvironmental Regulation in Autoimmunity and Cancer, 13125, Berlin, Germany., Wirges A; Max-Delbrück-Center for Molecular Medicine, MDC, Department of Translational Tumorimmunology, 13125, Berlin, Germany., Stark H; Max-Delbrück-Center for Molecular Medicine, MDC, Department of Translational Tumorimmunology, 13125, Berlin, Germany., Kretschmer V; Max-Delbrück-Center for Molecular Medicine, MDC, Department of Microenvironmental Regulation in Autoimmunity and Cancer, 13125, Berlin, Germany., Chmielewski M; Department I of Internal Medicine, University Hospital Cologne, 50931, Cologne, Germany., Uckert W; Max-Delbrück-Center for Molecular Medicine, MDC, Department of Molecular Cell Biology and Gene Therapy, 13125, Berlin, Germany., Abken H; RCI Regensburg Center for Interventional Immunology, Department Genetic Immunotherapy, University Hospital Regensburg, 93053, Regensburg, Germany., Westermann J; Department of Hematology, Oncology and Tumorimmunology, Campus Virchow Klinikum; Charité-University Medicine, 13353, Berlin, Germany., Rehm A; Max-Delbrück-Center for Molecular Medicine, MDC, Department of Translational Tumorimmunology, 13125, Berlin, Germany. arehm@mdc-berlin.de., Höpken UE; Max-Delbrück-Center for Molecular Medicine, MDC, Department of Microenvironmental Regulation in Autoimmunity and Cancer, 13125, Berlin, Germany. uhoepken@mdc-berlin.de.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2021 Jan 11; Vol. 12 (1), pp. 240. Date of Electronic Publication: 2021 Jan 11.
DOI:	10.1038/s41467-020-20488-3
Abstrakt:	CAR-T cell therapy targeting CD19 demonstrated strong activity against advanced B cell leukemia, however shows less efficacy against lymphoma with nodal dissemination. To target both B cell Non-Hodgkin's lymphoma (B-NHLs) and follicular T helper (Tfh) cells in the tumor microenvironment (TME), we apply here a chimeric antigen receptor (CAR) that recognizes human CXCR5 with high avidity. CXCR5, physiologically expressed on mature B and Tfh cells, is also highly expressed on nodal B-NHLs. Anti-CXCR5 CAR-T cells eradicate B-NHL cells and lymphoma-supportive Tfh cells more potently than CD19 CAR-T cells in vitro, and they efficiently inhibit lymphoma growth in a murine xenograft model. Administration of anti-murine CXCR5 CAR-T cells in syngeneic mice specifically depletes endogenous and malignant B and Tfh cells without unexpected on-target/off-tumor effects. Collectively, anti-CXCR5 CAR-T cells provide a promising treatment strategy for nodal B-NHLs through the simultaneous elimination of lymphoma B cells and Tfh cells of the tumor-supporting TME.
Databáze:	MEDLINE
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