Clinical trial landscape of CAR-based cell therapy for gastrointestinal malignancies

Gastrointestinal malignancies (GIM) impose a substantial global health burden, accounting for approximately 33% of cancer-related mortality worldwide. Although chimeric antigen receptor (CAR)-based cell therapy has achieved remarkable success in hematological malignancies, its application in solid tumors, particularly GIM, remains in its nascent stages. This comprehensive landscape analysis systematically examined the clinical trial ecosystem of CAR-based cell therapy for GIM by retrieving 179 eligible trials from the Trialtrove database as of October 2025 (hepatobiliary and pancreatic malignancies were excluded). The analysis revealed a predominantly early-phase landscape, with Phase I studies constituting 70.39% of all trials. Geographically, China (70.77%) and the USA (16.41%) dominated trial initiation, while academic institutions sponsored 54.92% of investigations. Claudin 18.2, NKG2D(L), mesothelin, and CEA emerged as the most frequently targeted antigens. Autologous therapy administered via peripheral intravenous infusion represented the predominant therapeutic modality. Combination strategies incorporating chemotherapy and immunotherapy demonstrated promising synergistic potential, suggesting that multimodal approaches may enhance therapeutic efficacy while potentially mitigating resistance mechanisms. The convergence of innovative preclinical developments with increasingly supportive regulatory frameworks portends transformative advances in the field, positioning CAR-based cell therapy as an emerging cornerstone modality in the therapeutic armamentarium against GIM.