A novel fourth generation of CAR-T cells: CD19 CAR-T cells engineered to express membrane-bound interleukin-15 and CXCR5 for the treatment of lymphoma.

ABSTRACT: The efficacy of CD19 CAR-T cells in B-cell lymphoma patients is not as good as that in B-cell acute lymphoblastic leukemia (B-ALL) patients. This might be attributed to the intricate tumor microenvironment of B-cell lymphoma, which leads to CAR-T cell exhaustion, inability to sustain function, and difficulty infiltrating into the tumor interior. We developed CD19 CAR structures that simultaneously produce membrane-bound IL-15 (mbIL-15) and CXCR5. This design aims to enhance the migration of CAR-T cells into CXCL13+ B-cell lymphomas and their long-term antitumor ability. Compared with CD19 CAR-T cells, CD19 mbIL15-CXCR5 CAR-T cells exhibited greater cytotoxicity against CD19+ tumor cell lines in vitro. In particular, when exposed to recurrent tumor antigen stimulation, CD19 mbIL15-CXCR5 CAR

SUBMITTER: Cao X 

PROVIDER: S-EPMC12553573 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature