tucidinostat + NKG2D CAR-NK cell therapy

Chidamide + NKG2D CAR-NK cell therapy is an investigational combination regimen being studied for the reduction of the latent HIV viral reservoir in individuals on stable antiretroviral therapy (ART). This approach utilizes a 'shock and kill' strategy: chidamide (tucidinostat), a selective histone deacetylase (HDAC) inhibitor, acts as a latency-reversing agent (LRA) to reactivate ('shock') latent HIV-1 from infected CD4+ T cells and upregulate NKG2D ligands on their surface. Subsequently, allogeneic natural killer (NK) cells engineered to express a chimeric antigen receptor (CAR) targeting NKG2D ligands (NKG2D/CD3ζ/DAP10) are administered to specifically recognize and eliminate ('kill') the reactivated, ligand-expressing infected cells. The therapy is currently being evaluated in a Phase I clinical trial (NCT03980691) sponsored by the First Affiliated Hospital of Zhejiang University.