Recent advances in the development of a Hepatitis C vaccine to prevent liver cancer were reviewed in the Therapeutic Cancer Vaccines conference held in Los Angeles April 27-29, 2003. This conference was sponsored by the John Wayne Cancer Institute, the Association of Biologics and the Royal Society of Medicine.

Hepatitis C affects approximately 170 million individuals world wide. Following acute infection, the virus persists in many patients and a minority can develop chronic disease. Chronic hepatitis can progress slowly over many decades to chronic active hepatitis and cirrhosis, ultimately leading to end stage liver disease or hepatocellular carcinoma. Approximately 20% of patients who develop cirrhosis will get cancer. It takes approximately 20 years to develop cirrhosis and 25-30 years to develop cancer. It is rare to develop hepatocellular carcinoma without cirrhosis.

The US is witnessing an increase in hepatitis C infection similar to the increase observed in Japan 50 years ago. Hepatitis C associated hepatocellular cancer is increasing in incidence while cancers related to alcohol and hepatitis B are remaining constant. There will be an expected 3-fold increase in hepatitis C associated liver cancer over the next 20 years.

Current treatment for hepatitis C consists of interferon alfa plus ribovarin. However, the response rate to interferon and ribovarin is only 50%. Currently, a large trial is being carried out in patients with cirrhosis to determine if 8 years of therapy with interferon alfa plus ribovarin prevents liver cancer.

Dr Michael Houghton of Chiron Corporation presented the current status of developing a vaccine against hepatitis C. ¹ The two hepatitis C vaccine strategies are 1) prophylactic vaccines to prevent infection and 2) therapeutic vaccines to prevent cirrhosis and cancer. The current clinical trial is testing a vaccine called E1E2/MF59 in chronically infected patients. This trial is approved by NIH and FDA. Chiron has another vaccine which uses a powerful saponin adjuvant which produces T-cell responses and promotes gamma interferon and TNF. This vaccine does not yet have regulatory approval for testing in humans.

There are many problems associated with developing hepatitis C vaccines. A major problem with vaccines is that it is “impossible to get budding and produce virus in culture” and the prime candidate vaccine “does not prime T lymphocytes”. Also, it is difficult to do testing since the chimpanzee is the only relevant animal. Furthermore, there are different strains of hepatitis C virus including 1A in the US and 1B throughout the world. There are also “differing subtypes and genotypes. Some antibodies do, however, cross react and there is cross binding.

Reference:

Houghton M, Hepatitis C Vaccines to Prevent Liver Cancer. Conference on the Development of Therapeutic Cancer Vaccines, Los Angeles CA April 27-29, 2008.