Hepatocellular Carcinoma Vaccine Hepatocellular cancer (HCC) is one of the most prevalent and lethal cancers worldwide and results in more than 600,000 global deaths per year. The main HCC-associated diseases are chronic infections with HBV and HCV. The most common and unifying condition associated with hepatocarcinogenesis is cirrhosis. HCC risk exponentially increases at the cirrhosis stage. In fact, HCC develops in a cirrhotic liver in 80% of cases – thus this pre-neoplastic condition is the strongest predisposing factor. Following curative treatment for HCC, 50%-90% of postoperative death is due to recurrent disease. Intra-hepatic recurrence is frequently the only site of reappearance. Currently, there is no consensus on a standard neoadjuvant, adjuvant or chemoprevention therapy for advanced HCC. Potential benefits of interferon (IFN) in preventing HCC recurrence after resection or ablation have been suggested by three randomized clinical trials. Adjuvant INF therapy is however fraught with serious dose-dependent toxicity. This program is focusing on the development of a novel therapeutic for the adjuvant treatment of advanced HCC. To this end, a therapeutic agent that would reduce both viral load and INF treatment associated systemic toxicity, would be ideal. A genetically engineered IBDV based vector vaccine seems to be such an agent. The product that VLI has under development is an orally-administered therapeutic vaccine utilizing an attenuated avian virus, the IBDV that causes no disease in humans. The recombinant IBDV used in this treatment modality is adapted to grow in Vero cells. IBDV is superior to other more developed vector candidates because (i) it has anti-HBV/HCV activity, (ii) it induces the regeneration of the liver, and (iii) as a B-lymphotrophic virus IBDV is shielded from virus-neutralizing antibodies allowing long-term maintenance of the therapy. IBDV can be engineered to deliver therapeutic proteins such as IFN‑α into the liver, frequently the only site of HCC reappearance. We hypothesize that the development of a recombinant IBDV vector therapy with localized interferon delivery could be administered long-term without systemic toxicity, thus it could save lives of many people with no other options available at present. The recombinant IBDV vector therapy may also have a preventive effect. To this end, in collaboration with University of Maryland Biotechnology Institute (UMBI), VectorLogics is developing second generation IBDV vectors. VLI intends to develop a well-characterized drug candidate that will result in an orally administered IBDV therapeutic vaccine vector expressing IFN‑α for the long-term adjuvant therapy of intra-hepatic recurrence of hepatocellular carcinoma.