Drug intelligence / Profile preview

tucidinostat + NKG2D CAR-NK cell therapy

Development stage
Unknown
Lead developer
First Affiliated Hospital, Zhejiang University School of Medicine
Modality
Small Molecules, CAR-NK Cells → Other Engineered Cells → Adoptive Cell Transfer → Cell Therapies, Lymphokine-Activated Killer Cells → Native Immune Cells → Adoptive Cell Transfer → Cell Therapies
Administration
Oral, Intravenous
01

Overview

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.

Other names
chidamide + NKG2D CAR-NK cell therapychidamide + NKG2D-directed chimeric antigen receptor natural killer cells
02

Targets

HDAC11 (Histone Deacetylase 11)MICB (Major histocompatibility complex class i-related protein B)HDAC10 (Histone Deacetylase 10)HDAC1 (Histone Deacetylase 1)HDAC8 (Histone Deacetylase 8)

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