DESCRIPTION: Hepatocellular cancer (HCC), with a global annual incidence of about 1.2 million new cases, represents one of the largest causes of cancer death in the world. Surgery is the only effective treatment and is available to and benefits only a very small minority of patients. No significant advances in the treatment of HCC have been made in the last two decades. Most HCC produce alpha fetoprotein (AFP), a 609 amino acid residue tumor marker. The applicants hypothesize that short AFP peptides, processed and presented by major histocompatibility class (MHC) molecules on the surface of HCC cells, can serve as suitable targets for an effective cell-mediated immune response against this tumor. They hypothesize that the human and murine T-cell repertoires have AFP peptide-responsive T cells that can be clonally expanded and activated under proper conditions. They propose a multipronged strategy with three Specific Aims to test this hypothesis with both murine and human HCC models.