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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., Pfeilschifter, J., Bluhm, J., Zschummel, M., Joedicke, J.J., Wirges, A., Stark, H., Kretschmer, V., Chmielewski, M., Uckert, W., Abken, H., Westermann, J., 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 |
| Number: | 1 |
| 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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