Cancer Vaccines in Hepatocellular Carcinoma: Advances, Challenges, and Future Perspectives

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, and therapeutic cancer vaccines have emerged as a promising immunotherapeutic strategy. These vaccines target tumor-associated antigens such as glypican-3, alpha-fetoprotein, melanoma-associate antigen-1, heat shock protein 70, glutamine synthetase, and TMEM176A/B, which are abnormally expressed in HCC cells and serve as both diagnostic markers and therapeutic targets. Various vaccine platforms—including peptide-based, dendritic cells-based, viral vector-based, and genetic vaccines (DNA/mRNA)—are under investigation for their ability to elicit antigen-specific cytotoxic T cell responses and establish long-term immune memory. Despite promising preclinical and early clinical results, challenges such as the immunosuppressive tumor microenvironment, antigen heterogeneity, and immune evasion mechanisms limit their efficacy. Future strategies focus on combination therapies with immune checkpoint inhibitors, personalized neoantigen vaccines, and advanced delivery technologies. These approaches aim to enhance immunogenicity and clinical outcomes, positioning therapeutic cancer vaccines as a key component of precision oncology in HCC.