Abstract: Chimeric antigen receptor T-cell (CAR-T) immunotherapy has emerged as a significant breakthrough in cancer treatment, demonstrating remarkable efficacy in hematological malignancies. However, its application in solid tumors, particularly hepatocellular carcinoma (HCC), faces numerous challenges. This review systematically summarizes recent research progress in CAR-T therapy for liver cancer, focusing on key target antigens such as glypican-3 (GPC3), alpha-fetoprotein (AFP), and epithelial cell adhesion molecule (EpCAM). Major limiting factors include tumor heterogeneity, the immunosuppressive tumor microenvironment (TME), treatment-related toxicities, and inadequate CAR-T cell infiltration. To address these bottlenecks, various optimization strategies are proposed, such as dual- or multi-targeting approaches, combination therapy regimens, and genetic engineering strategies to enhance CAR-T cell function. These advancements are anticipated to further improve the efficacy, safety, and accessibility of CAR-T therapy for liver cancer, potentially offering new hope for patients with advanced HCC. Future trends in CAR-T technology are expected to focus on intelligent CAR design, rational combination therapies, and the development ofin vivogenerated CAR-T cells. Finally, the ongoing challenges and potential solutions for CAR-T technology are outlined.

Key words: chimeric antigen receptor T cells, hepatocellular carcinoma, glypican-3, alpha-fetoprotein, epithelial cell adhesion molecule, tumor immunity