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Programming T Cells to Treat Liver Cancer

New therapy approach points to potential treatment of liver cancer patients with hepatitis B virus infection.

Chronic hepatitis B virus (HBV) infection is predominant in Asia and is highly associated with the development of hepatocellular carcinoma (HCC), a commonly occurring liver cancer.

The currently available effective treatments for small to moderate size HCC are restricted to surgery, liver transplantation and loco-regional treatment that kill cancer cells by interventional radiologic means, while treatment with drugs helps only in 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.

Researchers from Duke-NUS Medical School, Singapore General Hospital (SGH) and Lion TCR (a clinical-stage biotechnology company) have demonstrated that they were able to engineer HBV-specific T cells, a type of immune cells found in the body, to treat HCC. The treatment was also individualised, as T cells that were engineered were specific to the patients. The approach was successfully performed on two liver transplanted patients who had HBV associated liver cancer recurrence with one patient seeing a reduction in size of the tumour lesions.

“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. Hence, by analysing the specific HBV- DNA integration patterns in these HCC cells, we were able to select, design and engineer the individualised T cells for therapy. Our studies showed that these engineered T cells were able to destroy the tumour,” said Dr Antonio Bertoletti, professor of the Emerging Infectious Diseases (EID) Programme at Duke-NUS, Founder of the Singapore biotech company Lion TCR and co- author of the study.

The authors plan to further refine the technique and treatment strategy with further research study and trials to improve the efficacy of the therapy. [APBN]