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In vivo killing of primary HIV-infected cells by peripheral-injected early memory–enriched anti-HIV duoCAR T cells
- Anthony-Gonda, Kim;
- Ray, Alex;
- Su, Hang;
- Wang, Yuge;
- Xiong, Ying;
- Lee, Danica;
- Block, Ariele;
- Chilunda, Vanessa;
- Weiselberg, Jessica;
- Zemelko, Lily;
- Wang, Yen Y;
- Kleinsorge-Block, Sarah;
- Reese, Jane S;
- de Lima, Marcos;
- Ochsenbauer, Christina;
- Kappes, John C;
- Dimitrov, Dimiter S;
- Orentas, Rimas;
- Deeks, Steven G;
- Rutishauser, Rachel L;
- Berman, Joan W;
- Goldstein, Harris;
- Dropulić, Boro
- et al.
Published Web Location
https://doi.org/10.1172/jci.insight.161698Abstract
HIV-specific chimeric antigen receptor-T cell (CAR T cell) therapies are candidates to functionally cure HIV infection in people with HIV (PWH) by eliminating reactivated HIV-infected cells derived from latently infected cells within the HIV reservoir. Paramount to translating such therapeutic candidates successfully into the clinic will require anti-HIV CAR T cells to localize to lymphoid tissues in the body and eliminate reactivated HIV-infected cells such as CD4+ T cells and monocytes/macrophages. Here we show that i.v. injected anti-HIV duoCAR T cells, generated using a clinical-grade anti-HIV duoCAR lentiviral vector, localized to the site of active HIV infection in the spleen of humanized mice and eliminated HIV-infected PBMCs. CyTOF analysis of preinfusion duoCAR T cells revealed an early memory phenotype composed predominantly of CCR7+ stem cell-like/central memory T cells (TSCM/TCM) with expression of some effector-like molecules. In addition, we show that anti-HIV duoCAR T cells effectively sense and kill HIV-infected CD4+ T cells and monocytes/macrophages. Furthermore, we demonstrate efficient genetic modification of T cells from PWH on suppressive ART into anti-HIV duoCAR T cells that subsequently kill autologous PBMCs superinfected with HIV. These studies support the safety and efficacy of anti-HIV duoCAR T cell therapy in our presently open phase I/IIa clinical trial (NCT04648046).
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