Gregory P. Botta

Abstract Background Claudin18.2 (CLDN18.2) is a tight junction protein found in gastric epithelial cells. It can become abnormally expressed in gastric cancer and other solid tumors, rendering it a candidate for targeted therapy. There are no approved therapeutic agents against CLDN18.2. The T cell antigen coupler (TAC) technology modifies T cells ex vivo, allowing cytotoxicity of tumor cells by co–opting the natural T cell receptor.

Discussion Prior reports of solid tumor CAR-T-cell trials showed substantial toxicities including CRS, ICANS, hematologic and on-target, off-tumor toxicities.16 For example, a HER2-directed CAR-T-cell treatment-related death occurred in a colon cancer patient with lung and liver metastasis due to cytokine storm.15 Here, Patient 1 had manageable side effects with CT041, possibly due to the restricted expression of CLDN18.2 in normal tissues.