Bunse, Mario and Pfeilschifter, Janina and Bluhm, Julia and Zschummel, Maria and Joedicke, Jara J. and Wirges, Anthea and Stark, Helen and Kretschmer, Vivien and Chmielewski, Markus and Uckert, Wolfgang and Abken, Hinrich and Westermann, Joerg and Rehm, Armin and Hoepken, Uta E. (2021) CXCR5 CAR-T cells simultaneously target B cell non-Hodgkin's lymphoma and tumor-supportive follicular T helper cells. NATURE COMMUNICATIONS, 12 (1): 240. ISSN 2041-1723
Full text not available from this repository. (Request a copy)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. CAR-T cell therapy targeting CD19 is not as efficient to treat lymphoma with nodal dissemination as it is for B cell leukaemia. Here, the authors generate CAR-T cells against CXCR5 and show they inhibit tumour growth by depleting both B and follicular T helper cells in lymphoma models.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHRONIC LYMPHOCYTIC-LEUKEMIA; CHEMOKINE RECEPTOR; MATURATION ANTIGEN; THERAPY; MICROENVIRONMENT; EXPRESSION; IMMUNOTHERAPY; ACTIVATION; RITUXIMAB; SURVIVAL |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Sep 2022 05:44 |
| Last Modified: | 08 Sep 2022 05:44 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47499 |
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