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.