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| Item Type: | Article |
|---|---|
| Title: | Engineered CCR7 overexpression enhances nodal CAR T-cell homing and cytotoxicity toward B-cell lymphoma |
| Creators Name: | Zschummel, Maria, Bunse, Mario, Spierling, Anna-Lena, Li, Anna, Joedicke, Jara J., Margineanu, Anca, Blachut, Susanne, Lindberg, Eric Lars-Helge, Ruiz-Orera, Jorge, Hübner, Norbert, Rehm, Armin and Höpken, Uta E. |
| Abstract: | Anti-CD19 chimeric antigen receptor (CAR) therapy demonstrated remarkable efficacy against hematologic malignancies. However, B-cell malignancies with lymph node (LN) involvement frequently remain resistant. In this study, we show that CAR T cells downregulated the chemokine receptor CCR7, crucial for nodal homing, during manufacturing. Consequently, in vitro migration toward the respective chemokines and in vivo migration to LNs was severely impaired. To improve nodal CAR T-cell trafficking, we engineered anti-CXCR5 CAR T cells, targeting mature lymphoma, with stable CCR7 expression (CAR.CCR7). CCR7 engineering of human and mouse CAR T cells restored migratory capacity and LN homing. Additionally, we observed enhanced CAR-mediated killing in CCR7-engineered anti-CXCR5 and anti-CD19 CARs alike, a process that was independent of increased cytokine secretion. Mechanistically, CCR7 overexpression was associated with an altered expression of genes involved in cytoskeletal rearrangement and faster killing kinetics. CCR7 accumulated in mature CAR synapses, supporting the costimulatory role of CCR7 within immunologic synapses. Therapeutically, improved LN recruitment and enhanced killing of CAR.CCR7 T cells improved lymphoma eradication in mice. |
| Keywords: | Adoptive Immunotherapy, B-Cell Lymphoma, CCR7 Receptors, Cell Movement, Chimeric Antigen Receptors, Immunologic Cytotoxicity, Lymph Nodes, T-Lymphocytes, Tumor Cell Line, Animals, Mice |
| Source: | Cancer Immunology Research |
| ISSN: | 2326-6066 |
| Publisher: | American Association for Cancer Research |
| Volume: | 14 |
| Number: | 5 |
| Page Range: | 827-844 |
| Date: | 4 May 2026 |
| Official Publication: | https://doi.org/10.1158/2326-6066.cir-25-1381 |
| PubMed: | View item in PubMed |
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