Yonsei Cancer Hospital develops CAR-T therapy for ovarian and gastric cancers

A research team at Yonsei Cancer Hospital has developed a next-generation CAR-T cell therapy targeting solid tumors, specifically ovarian and gastric cancers. By identifying the L1CAM protein as a target, the researchers addressed a major limitation of current CAR-T therapies, which have historically been more effective against blood cancers than solid tumors due to difficulties in target identification and tumor penetration.

Analysis of tumor tissues from 227 ovarian cancer patients and 132 gastric cancer patients revealed high L1CAM expression in approximately 37% and 22% of cases, respectively. High L1CAM expression was linked to shorter overall survival rates. The team engineered CAR-T cells to selectively recognize L1CAM, enhancing their anti-cancer effects by combining CD28 and ICOS costimulatory factors.

In animal models using tumors transplanted from actual patients, a single low dose of the developed CAR-T therapy resulted in the complete disappearance of ovarian tumors. The therapy also demonstrated tumor suppression in gastric cancer models. For ovarian cancer, direct intraperitoneal administration proved more effective and sustained than intravenous administration. The study's findings were published in the Journal for ImmunoTherapy of Cancer.