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

Abstract CAR-T cell therapy targeting CD19 demonstrated strong activity against advanced B leukemia, however shows less efficacy lymphoma with nodal dissemination. To target both Non-Hodgkin’s (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 high avidity. CXCR5, physiologically expressed on mature Tfh cells, is also highly B-NHLs. Anti-CXCR5 eradicate B-NHL lymphoma-supportive more potently than vitro, they efficiently inhibit growth murine xenograft model. Administration of anti-murine syngeneic mice specifically depletes endogenous malignant without unexpected on-target/off-tumor effects. Collectively, anti-CXCR5 provide promising treatment strategy for B-NHLs through simultaneous elimination tumor-supporting TME.