​In a move that will bring hope to liver transplant patients around the world, Lion TCR, a Singapore biotechnology company, has signed an exclusive worldwide licensing agreement with Duke-NUS Medical School to develop an innovative method of using gene-edited T cells to treat recurring cancers in the donated organ.
Developed by Professor Antonio Bertoletti and his colleagues Anthony Tan and Morteza Hefezi from Duke-NUS’ Emerging Infectious Diseases Programme, this novel method uses T cells that have been bioengineered to be shielded from the immunosuppressant drugs these patients are required to take to avoid organ rejection. Armoured like that, the T cells can destroy the cancer cells without being hindered.

By combining this novel gene-editing technology with the company’s propriety library of T cell receptors (TCRs), Lion TCR aims to further enhance TCR therapy for liver cancer and other diseases. The modified T cells could also be used to treat other common conditions associated with immunosuppressant treatment, such as the reactivation of Epstein Barr Virus or cytomegalovirus in patients receiving immunosuppressants after stem cell or organ transplantation.

Hepatocellular carcinoma is the most common type of primary liver cancer and the sixth most common cancer worldwide. It often develops in people with chronic liver disease following hepatitis B infection.

A common treatment for hepatocellular carcinoma is to completely remove the liver and replace it with a healthy one from a donor. However, hepatitis B-related hepatocellular carcinoma can recur in some patients following transplantation. To kill the cancer, doctors can inject T cells, which are specially designed to target hepatitis B material found in the cancer cells. However, liver transplant patients must take drugs that suppress their immune systems to prevent their bodies from attacking the transplants. This significantly hinders the effectiveness of T-cell therapy.

To overcome this limitation, Prof Bertoletti and his team further modified the T cells by gene editing, to disrupt the functions of enzymes involved in the metabolism of immunosuppressant drugs. Based on findings published in Hepatology (M Hafezi et al, Immunosuppressive Drug Resistant Armored TCR T cells for immune-therapy of HCC in liver transplant patients. Hepatology 2020. doi:10.1002/hep.31662.), these “armoured” T cells were effective at killing liver cancer cells for up to four days even in the presence of immunosuppressive drugs.

Dr Peng Xiaoming, CEO of Lion TCR, said, “This new technology can potentially unleash a wide range of applications of new TCR-T cell products for Lion TCR. We are very excited with this addition to our product development pipeline and to eventually bring them forward for patient care!”

Mr David Wang, Director of Centre for Technology and Development at Duke-NUS, added, “This collaboration between Duke-NUS and LionTCR will enable new T cell therapies to be used in patients who might otherwise not have access to this exciting new cancer treatment because of their concurrent need for immunosuppressive drugs."