A novel FITC.Chimeric antigen receptor-T cell targeting HIV-1-infected cells with FITC-conjugated antibodies for enhanced cytotoxicity.

HIV-1 persists as a global health burden due to latent reservoirs and immune evasion that undermine eradication efforts, even under antiretroviral therapy (ART). To address this challenge, we developed a novel FITC.CAR strategy, incorporating an anti-FITC single-chain variable fragment (scFv), to selectively target HIV-1-infected cells when conjugated with FITC-labeled broadly neutralizing antibodies (bNAbs). FITC.CAR-T cells achieved up to ~70 % cytotoxicity against HIV-1-infected CD4+ T cells across subtypes B, C, and O, and demonstrated markedly enhanced clearance of reactivated latent HIV-1 reservoirs in both viral latent cell lines and CD4+ T cells derived from HIV-infected patient with ART compared to controls. In a humanized BLT mouse model, this strategy led to an approximate 90 % reduction in HIV-1 loads after ART interruption. By coupling the specificity of bNAbs with the cytolytic power of CAR-T cells, this strategy offers a flexible and effective platform for achieving a functional HIV-1 cure.