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CXCR5+ anti-Env CAR T cells represent an investigational chimeric antigen receptor (CAR) T-cell therapy designed to target the latent HIV-1 reservoir. Developed by researchers at LMU Klinikum, the German Center for Infection Research (DZIF), and collaborating institutions, this therapy addresses a major barrier to an HIV cure: the persistence of latently infected CD4+ T cells in B-cell follicles of secondary lymphoid tissues, which are largely inaccessible to conventional cytotoxic T cells. The primary CD8+ T cells are engineered via lentiviral transduction to co-express CXCR5—a chemokine receptor that directs homing to B-cell follicles via the CXCL13 gradient—and an anti-Env CAR utilizing the antigen-binding domain of the CD4-binding site-directed broadly neutralizing antibody (bnAb) 3BNC117. In preclinical studies, these dual-engineered CAR T cells demonstrated directed migration toward CXCL13 and potent in vitro cytotoxicity, eliminating up to 70% of HIV-1-infected primary CD4+ T cells and showing efficacy in biomimetic tonsil organoid models.
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