Definition

A preparation of T lymphocytes that have been genetically modified to express chimeric antigen receptors (CARs) targeting the tumor-associated antigen (TAA) Claudin18.2 (CLDN18.2; A2 isoform of claudin-18) and the immunosuppressive ligand programmed cell death-1 ligand 1 (PD-L1; cluster of differentiation 274; CD274), with potential immunostimulating and antineoplastic activities. Upon administration, anti-CLDN18.2/anti-PD-L1 CAR-T cells target and bind to CLDN18.2- and PD-L1-expressing tumor cells, thereby inducing selective toxicity in CLDN18.2- and PD-L1-expressing tumor cells. CLDN18.2, a tight junction protein and stomach-specific isoform of claudin-18, 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. PD-L1, which is overexpressed in many human cancer cell types, plays an important role in the downregulation of the immune system and tumor evasion from host immunity.