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To increase the immunosurveillance in HIV infection, we used retroviral vectors expressing CD4‐chimeric antigen receptors (CARs) to genetically modify autologous T cells and redirect CTL toward HIV. The CD4 extracellular domain targets envelope and the intracellular signaling domains activate T cells. The maC46 fusion inhibitor binds HIV and blocks viral replication.

We stimulated rhesus PBMCs with antibodies to CD3/CD28 and cotransduced T cells with CD4‐CAR and maC46 vectors. CD4‐CAR‐transduced T cells were added to Env⁺ 293T cells at E:T of 1:1. Killing of target cells was measured as reduced impedance.

We observed gene expression in 60–70% of rhesus CD3⁺CD8⁺ T cells with the individual vectors and in 35% of the cells with both vectors. CD4‐CAR‐transduced populations specifically killed Env⁺ cells.

In these studies, we showed that …