Allogeneic gene-edited HIV-specific CAR-T cells secreting PD-1 blocking scFv enhance specific cytotoxic activity against HIV Env⁺ cells invivo.

ABSTRACT: HIV-specific chimeric antigen receptor (CAR) T-cells have been developed to target HIV-1 infected CD4⁺ T-cells that express HIV Env proteins. However, T cell exhaustion and the patient-specific autologous paradigm of CAR-T cell hurdled clinical applications. Here, we created HIV-specific CAR-T cells using human peripheral blood mononuclear cells and a 3BNC117-E27 (3BE) CAR construct that enabled the expression of programmed cell death protein (PD-1) -blocking scFv E27 and the single-chain variable fragment of the HIV-1-specific broadly neutralizing antibody 3BNC117 to target native HIV Env. Compared with T cells expressing 3BNC117-CAR alone, 3BE CAR-T cells showed greater cytotoxic activity against HIV Env⁺ cells with stronger proliferation capability, higher killing

SUBMITTER: Pan H 

PROVIDER: S-EPMC10176442 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature