Liu B, Zhang W, Xia B, et al. Broadly Neutralizing Antibody-Derived CAR-T Cells Reduce Viral Reservoir in HIV-1-Infected Individuals. Journal of Clinical Investigation. 2021; (doi: 10.1172/JCI150211).
Adoptive transfer of a broadly neutralizing antibody (bNAb)-derived CAR T cell therapy that can apply specific cytotoxic activity against HIV-1-infected cells was safe and reduced viral reservoirs, new research shows. The open-label study involved participants infected with HIV-1 who were undergoing analytical interruption of antiretroviral therapy (ART). In all, 14 individuals received a single administration of bNAb-derived CAR T cells. The treatment was well tolerated. Among the six patients who discontinued ART, viremia rebound occurred within a median 5.3 weeks. The rebounds were all the result of preexisting or emerging viral escape mutations. Following CAR T cell treatment, there were significant reductions in cell-associated viral RNA and intact proviruses. Evaluations of HIV-1 variants prior to or following CAR T administration indicate that CAR T cells applied pressure on rebound viruses. This, in turn, resulted in a number of viruses with reduced diversity and mutations against CAR-T-mediated cytotoxicity.