Researchers design armored immune cells to attack recurrent cancer in liver transplant patients

Researchers at the Duke-NUS School of Medicine, together with colleagues in Singapore, have designed armored immune cells that can attack recurrent cancer in liver transplant patients, while patients with immunosuppressive drugs avoided for a time to avoid organ rejection. The findings were published in the journal Hepatology.

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 after hepatitis B infection.

A common treatment for hepatocellular carcinoma is to completely remove the liver and remove a healthy one from a donor. However, hepatocellular carcinoma associated with hepatitis B can recur in some patients after transmission. To kill the cancer, doctors can inject immune cells, called T cells, that are specifically designed to target hepatitis B material found in the cancer cells. However, liver transplant patients need to take drugs that destroy their immune systems to prevent their bodies from attacking the transplants. This significantly limits the effectiveness of T cell therapy.

“We developed a method to make T cells that specifically target hepatitis B antigen in liver cancer cells and, at the same time, stabilize them against two common immunosuppressants: tacrolimus and mycophenolate mofetil,” the Dr. Antonio Bertoletti, senior author of the study from Duke-NUS ’Emerging Infectious Diseases Program.

“Importantly, our T-cell resistance to the vaccines lasted only about four days after regaining sensitivity to the drugs,” said Dr. Bertoletti.

This non-invasive effect, due to the engineering approach used by the team, provides an additional layer of safety so that organ recurrence can be minimized.

Professor Bertoletti and his colleagues began the study by testing the effects of tacrolimus and mofetil mycophenolate on T cells designed with specific receptors targeting hepatitis B antigens located on cancer cells liver. They found that both drugs significantly reduced the ability of T cells to kill the cancer cells.

The team then remodeled the T cells by inserting genetic codes that disrupt the enzymes needed by both drugs to suppress immune cells. They found that the infectious T cells of hepatitis BT cell (IDRA HBV-TCR) T cell showed the “positive killing” power of hepatocellular carcinoma cell targets for up to four days.

“We also found that this strategy can be applied to target other pathologies that typically occur in referral patients receiving immunosuppressive drugs, such as the Epstein virus. -Top and cytomegalovirus reactions, “said Dr. Anthony T Tan, senior researcher in Professor Bertoletti’s laboratory and co-author of the study.

Innovative research like this lays the foundation for new discoveries and transformational change. With waiting lists for organs expanding all over the world, ensuring that those patients who are benefiting from a much-needed transplant can stay in relief. is a great improvement and offers a lot of hope. “

Professor Patrick Casey, Senior Deputy Dean for Research, Duke-NUS School of Medicine

The team’s next goal is to use their approach in clinical trials.