Novel Cellular Therapies for Hepatocellular Carcinoma

SIMPLE SUMMARY: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related death worldwide. Most patients present with incurable disease and the prognosis remains poor. Immunotherapy using immune checkpoint inhibitors has become standard of care for advanced disease but only a minority respond, and novel approaches are needed. Cell based immune therapies have proven efficacy in haematological cancers and are currently being evaluated in solid tumours including HCC. Examples include Chimeric Antigen Receptor T cells (CAR-T) and T-cell receptor engineered T-cells (TCR-T). Here, we review the landscape of cellular immunotherapy for HCC, and outline how advanced engineering solutions may further enhance this therapeutic approach. ABSTRACT: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related death worldwide. Most patients present with advanced disease, and current gold-standard management using tyrosine kinase inhibitors or immune checkpoint inhibitors (ICIs) offers modest clinical benefit. Cellular immune therapies targeting HCC are currently being tested in the laboratory and in clinical trials. Here, we review the landscape of cellular immunotherapy for HCC, defining antigenic targets, outlining the range of cell therapy products being applied in HCC (such as CAR-T and TCR-T), and exploring how advanced engineering solutions may further enhance this therapeutic approach.