Broadly neutralizing antibody derived CAR T cells reduce viral reservoir in individuals infected with HIV-1

BACKGROUND. Chimeric antigen receptor (CAR) T cells have emerged as an approach to treat malignant tumors. This strategy has also been proposed for the treatment of HIV-1 infection. We have developed a broadly neutralizing antibody-derived (bNAb-derived) CAR T cell therapy that can exert specific cytotoxic activity against HIV-1-infected cells. METHODS. We conducted an open-label trial of the safety, side-effect profile, pharmacokinetic properties, and antiviral activity of bNAb-derived CAR T cell therapy in individuals infected with HIV-1 who were undergoing analytical interruption of antiretroviral therapy (ART). RESULTS. A total of 14 participants completed only a single administration of bNAb-derived CART cells. CAR T cell therapy administration was safe and well tolerated. Six participants discontinued ART, and viremia rebound occurred in all of them, with a 5.3-week median time. Notably, the cell-associated viral RNA and intact proviruses decreased significantly after CAR T cell treatment. Analyses of HIV-1 variants before or after CART cell administration suggested that CART cells exerted pressure on rebound viruses, resulting in a selection of viruses with less diversity and mutations against CART cell-mediated cytotoxicity. CONCLUSION. No safety concerns were identified with adoptive transfer of bNAb-derived CAR T cells. They reduced viral reservoir. All the rebounds were due to preexisting or emergence of viral escape mutations.

Automated summary

This study investigated the safety and antiviral activity of bNAb-derived CAR T cell therapy in individuals infected with HIV-1 undergoing analytical interruption of antiretroviral therapy. The therapy was found to be safe and effective, reducing viral reservoir, but rebound was due to viral escape mutations.