Hepatocellular carcinoma (HCC) remains a formidable global health challenge, representing a leading cause of cancer-related mortality with limited effective therapeutic options for advanced stages. While conventional treatments have shown some efficacy, the inherent aggressive nature and complex tumor microenvironment of HCC necessitate innovative approaches. Chimeric Antigen Receptor (CAR) T-cell therapy has revolutionized the treatment landscape for hematological malignancies, demonstrating profound and durable responses. However, its translation to solid tumors, including HCC, has encountered significant hurdles, such as the lack of specific tumor antigens, an immunosuppressive tumor microenvironment, and the risk of on-target, off-tumor toxicities. This review provides a comprehensive overview of the recent advancements in CAR T-cell therapy specifically tailored for HCC, highlighting promising target antigens identified to date, discussing the design strategies employed to enhance their efficacy, and outlining the persistent challenges that require innovative solutions. Understanding the current progress and remaining obstacles is crucial for guiding future research and realizing the full therapeutic potential of CAR T cells in the fight against HCC.

Hepatocellular Carcinoma, CAR T-cell therapy, Immunotherapy

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olid Tumors, Tumor Antigens, Adoptive Cell Therapy.