CAR-T Therapy for the Treatment of Colorectal Cancer

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Advanced CRC has a poor prognosis, with treatment primarily relying on chemotherapy combined with targeted therapies. Currently, immunotherapy based on immune checkpoint inhibitors is reserved exclusively for mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) tumors, which represent less than 10% of advanced CRC cases. Chimeric antigen receptor (CAR)-T cell therapy is a type of adoptive cell therapy involving modified T-lymphocytes engineered to express chimeric antigen receptors, enabling them to recognize surface antigens expressed by tumor cells. CAR-T cell therapy has demonstrated efficacy in treating hematological malignancies such as lymphoma, myeloma, and leukemia. However, its efficacy in solid tumors remains limited due to several limitations such as antigen heterogeneity, restricted CAR-T cell trafficking into the tumor area, and the presence of an immunosuppressive tumor microenvironment. Developing novel CAR-T cell therapies for solid tumors represents an unmet need, particularly for cases where immune checkpoint blockade is ineffective, such as CRC. Preclinical studies have shown the efficacy of various CAR-T cell models targeting a wide range of tumor-associated antigens in CRC, both in vitro and in vivo. Despite these promising results, the clinical efficacy of CAR-T cell therapy for CRC has been limited in early-phase clinical trials. Factors such as trial design or tumor characteristics, including antigen heterogeneity and the immunosuppressive microenvironment, should be considered. The development of innovative CAR-T cell models and the identification of novel antigens may improve the effectiveness of CAR-T cell therapy for CRC patients.