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Chimeric antigen receptor (CAR)-T cells, which have shown success in the treatment of blood cancers, could potentially eradicate HIV infection. Anthony-Gonda et al. have designed HIV-1-specific CAR-T cells based on a two-molecule CAR architecture, termed duoCAR, which targets multiple sites on the HIV envelope glycoprotein. In vitro, the duoCAR-T cells exerted broad and potent killing of HIV-infected blood cells. Notably, the duoCAR-T cells themselves were resistant to HIV infection. In a humanized mouse model of intrasplenic HIV infection, the duoCAR-T cells exerted long-term control of HIV infection and prevented loss of CD4+ T cells.
Anthony-Gonda, K. et al. Multispecific anti-HIV duoCAR-T cells display broad in vitro antiviral activity and potent in vivo elimination of HIV-infected cells in a humanized mouse model. Sci. Transl Med.11, eaav5685 (2019)