Skip to main content
drug_type
RELEVANT_DRUG
intervention_type
Cellular gene therapy (CAR T cells)
drug_description
Autologous, genetically modified CAR T-cell therapy engineered to dual-target NKG2D ligands (e.g., MICA/MICB/ULBP family) and CLDN18.2 on tumor cells, activating T-cell cytotoxicity to treat advanced NKG2DL+/CLDN18.2+ solid tumors.
nci_thesaurus_concept_id
C192807
nci_thesaurus_definition
A preparation of autologous T-lymphocytes that have been genetically modified to express a tandem chimeric antigen receptor (CAR) targeting the tumor-associated antigens (TAAs) natural-killer group 2, member D ligands (NKG2DLs) and Claudin18.2 (CLDN18.2; A2 isoform of claudin-18), with potential immunostimulating and antineoplastic activities. Upon administration, autologous anti-NKG2DL/anti-CLDN18.2 bispecific CAR-T cells KD-496 specifically and simultaneously recognize and induce selective toxicity in tumor cells expressing NKG2DLs and CLDN18.2. Ligands for NKG2D, such as MHC class I chain-related protein A (MICA), MICB, and members of the UL16-binding proteins (ULBP)/retinoic acid early transcript 1 (RAET1) family, are overexpressed on infected cells and most cancer cell types, but are not expressed on most normal, healthy cells. CLDN18.2, a tight junction protein, is expressed on a variety of tumor cells, but its expression in healthy tissues is strictly confined to short-lived differentiated epithelial cells of the gastric mucosa.
drug_mesh_term
Chimeric Antigen Receptor T-Cell Therapy
drug_category
CAR T
drug_class
Cellular Therapy
drug_delivery_route
Intravenous
drug_mechanism_of_action
Autologous T cells engineered with a tandem/bispecific CAR that recognizes NKG2D ligands (e.g., MICA, MICB, ULBP family) and CLDN18.2 on tumor cells. Target engagement activates CAR signaling, leading to T-cell cytotoxic killing via perforin/granzyme release and cytokine production, selectively lysing NKG2DL+/CLDN18.2+ cancer cells.
drug_name
KD-496
nct_id_drug_ref
NCT06134960