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

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Item Type:Article
Title:CXCR5 CAR-T cells simultaneously target B cell non-Hodgkin's lymphoma and tumor-supportive follicular T helper cells
Creators Name:Bunse, M. and Pfeilschifter, J. and Bluhm, J. and Zschummel, M. and Joedicke, J.J. and Wirges, A. and Stark, H. and Kretschmer, V. and Chmielewski, M. and Uckert, W. and Abken, H. and Westermann, J. and Rehm, A. and Höpken, U.E.
Abstract: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.
Keywords:B-Lymphocytes, Cell Proliferation, Cell Survival, Chimeric Antigen Receptors, CXCR5 Receptors, HEK293 Cells, Helper-Inducer T-Lymphocytes, Hep G2 Cells, Human Umbilical Vein Endothelial Cells, Neoplasm Antigens, Neoplasms, Non-Hodgkin Lymphoma, T-Lymphocytes, Tumor Cell Line, Xenograft Model Antitumor Assays, Animals, Mice
Source:Nature Communications
ISSN:2041-1723
Publisher:Nature Publishing Group
Volume:12
Page Range:240
Date:11 January 2021
Official Publication:https://doi.org/10.1038/s41467-020-20488-3
PubMed:View item in PubMed

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