Development of a recombinant murine tumor model using hepatoma cells expressing hepatitis C virus (HCV) non-structural antigens

Hepatitis C virus (HCV) chronically infects 2-3% of the world's population, causing liver disease and cancer with prolonged infection. The narrow host range of the virus, being restricted largely to human hepatocytes, has made the development of a relevant infection and reliable model to evaluate the efficacy of vaccines a challenge. We have developed a novel approach to accomplish this by generating a murine hepatoma cell line stably expressing non-structural HCV antigens which can be used in vitro or in vivo to test HCV vaccine efficacies. These HCV-recombinant hepatoma cells formed large solid-mass tumors when implanted into syngeneic mice, allowing us to test candidate HCV vaccines to demonstrate the development of an HCV-specific immune response that limited tumor growth. Using this model, we tested the therapeutic potential of recombinant anti-HCV-specific vaccines based on two fundamentally different attenuated pathogen vaccine systems - attenuated Salmonella and recombinant adenoviral vector based vaccine. While attenuated Salmonella that secreted HCV antigens limited growth of the HCV-recombinant tumors when used in a therapeutic vaccination trial, replication-competent but non-infectious adenovirus expressing non-structural HCV antigens showed overall greater survival and reduced weight loss compared to non-replicating non-disseminating adenovirus. Our results demonstrate a model with antitumor responses to HCV NS protein antigens and suggest that recombinant vaccine vectors should be explored as a therapeutic strategy for controlling HCV and HCV-associated cancers. This article is protected by copyright. All rights reserved.