CAR T-cell therapy, initially successful in blood cancers, is showing promise in solid tumors like gastric and esophageal cancers. This therapy engineers a patient’s T-cells to recognize and attack cancer, but solid tumors present unique challenges. Tumor antigens can vary, making it hard to target cancer without affecting healthy tissue. The dense tumor microenvironment suppresses T-cell activity and limits penetration, and manufacturing CAR T-cells is time-consuming and costly.
Despite these hurdles, progress is being made. Claudin 18.2 (CLDN18.2) is a key target in gastric and gastroesophageal cancers. In the CT041 Phase 2 trial, patients receiving CLDN18.2-targeting CAR T-cells had twice the progression-free survival compared to standard therapy. HER2, CEA, MUC1, and EpCAM are also being explored as CAR T-cell targets in these cancers.
Future developments include next-generation CAR T-cells designed to overcome tumor immune suppression, allogeneic “off-the-shelf” therapies to reduce cost and time, and combination strategies with checkpoint inhibitors or chemotherapy. Early results suggest CAR T-cell therapy could become a valuable option for difficult-to-treat gastric and esophageal cancers.