Engineering T-Cells To Home In On Liver Cancer

Researchers in Singapore have selected, designed and engineered patient-specific T cells that target hepatitis B-infected liver cancer cells.

AsianScientist (Apr. 10, 2019) – By engineering T-cells that specifically target the hepatitis B virus (HBV), scientists in Singapore have found a way to treat liver cancer. Their findings are published in the journal Gastroenterology.

Chronic HBV infection is predominant in Asia and is highly associated with the development of hepatocellular carcinoma (HCC), a common form of liver cancer. Currently, the treatment options available to patients diagnosed with HCC include surgery, liver transplantation, radiation therapy and chemotherapy.

To widen the treatment arsenal against HCC, researchers from the Duke-National University of Singapore Medical School (Duke-NUS), Singapore, with collaborators at the Singapore General Hospital (SGH) and biotech company Lion TCR, sought to leverage the immune system to destroy liver cancer cells. They engineered T-cells, a type of immune cells found in the body, to home in on HBV.

“We showed that integrated HBV-DNA gene components in the HCC cells were able to activate functional HBV-specific T-cells. 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,” said Dr. Antonio Bertoletti, professor of the Emerging Infectious Diseases Program at Duke-NUS and founder of Lion TCR.

The researchers tested their therapy in two liver transplant patients who had HBV-associated liver cancer recurrence and observed a reduction in size of the tumor lesions in one patient.

“There were over 20 T-cell infusions that were successfully performed on the two liver- transplanted patients. 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,” said Dr. Thinesh Lee Krishnamoorthy, consultant, department of gastroenterology and hepatology at SGH, who co-authored the study.

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

The article can be found at: Tan et al. (2019) Use of Expression Profiles of HBV-DNA Integrated Into Genomes of Hepatocellular Carcinoma Cells to Select T Cells for Immunotherapy.


Source: Duke-NUS Medical School; Photo: Shutterstock.
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