Researchers have engineered hepatitis B virus-specific T cells, a type of immune cell found in the body, to treat hepatocellular carcinoma, a commonly occurring liver cancer.
The researchers also individualized the treatment, making the T cells specific to the patients. The team successfully performed the approach on two liver transplanted patients who had hepatitis B virus (HBV) associated liver cancer recurrence, with one patient seeing a reduction in size of the tumor lesions.
Chronic HBV infection is predominant in Asia and is highly associated with the development of hepatocellular carcinoma (HCC), a commonly occurring liver cancer. The current effective treatments for small to moderate size HCC include only surgery, liver transplantation, and loco-regional treatment that kill cancer cells by interventional radiologic means. Treatment with drugs only leads to a modest increase in the overall survival in more extensive disease. In patients who have HCC recurrence after liver transplantation, the treatment options are even more limited.
“In this study we showed that the integrated HBV-DNA gene components in the HCC cells were able to activate functional HBV-specific T cells,” says senior coauthor Antonio Bertoletti, a professor from the emerging infectious diseases program at Duke-NUS Medical School.
“Hence, by analyzing the specific HBV-DNA integration patterns in these HCC cells, we were able to select, design, and engineer the individualized T cells for therapy. Our studies showed that these engineered T cells were able to destroy the tumor.”
“There were over 20 T cell infusions that were successfully performed on the two liver-transplanted patients,” says coauthor Thinesh Lee Krishnamoorthy, a consultant in the gastroenterology and hepatology department at Singapore General Hospital (SGH). “None of the patients experienced adverse reactions related to the treatment and one of them had a reduction in the tumor size of distant metastases of the liver cancer.
“Given that 80 percent of the HCC cases in Asia are currently HBV-related, this approach could lead to a major breakthrough in improving the survival and quality of life of patients suffering from this disease.”
The authors plan to further refine the technique and treatment strategy with further research and trials to improve the efficacy of the therapy.
Additional researchers who contributed to the work came from Duke-NUS; SGH; and Singapore biotech company Lion TCR.