A research team at UCLA has developed a new method to prompt the immune system to target and kill cells infected with cytomegalovirus (CMV), a virus that poses serious risks to immunocompromised individuals, such as organ transplant recipients and people with AIDS. CMV can also cause deafness in infants if transmitted from mother to child during pregnancy.
The team engineered antibodies that direct T-cells—key components of the immune system—to attack CMV-infected cells. Current treatments for CMV are costly and can have severe side effects, including bone marrow suppression and kidney damage. There is also a risk of the virus developing resistance to these drugs.
“This is a potentially new way to harness the immune system against this virus and could offer new opportunities to treat transplant patients or AIDS patients with life-threatening infection, or children with poorly controlled infection that puts them at risk for deafness,” Yang said.
The findings are published in Science Advances, a peer-reviewed journal.
Typically, people with healthy immune systems carry CMV without symptoms for life. Drugs exist for prevention and treatment but often come with significant drawbacks. Another approach—adoptive transfer of expanded patient-specific CMV-killing T-cells—demonstrates the importance of T-cell immunity but is too slow for urgent cases. Similarly, CAR-T therapy faces time constraints when dealing with acute infections.
Researchers explored an alternative: T-cell redirecting bispecific antibodies (TRBAs). These have previously been used in cancer therapies, but their application against viral infections like CMV is relatively new. The UCLA team designed TRBAs by engineering antibodies that link CD3-epsilon on CD8+T-cells (CTLs) directly to a viral protein present on infected cells. This connection prompts CTLs to cluster around and destroy the infected cell.
“Hopefully, if there is commercial interest, these antibodies could be tested in clinical trials,” Yang said.
The study was supported through philanthropic donations rather than grant funding. The research team included Ayub Ali, Arumugam Balamurugan, F. Javier Ibarrondo , Minh Nguyen, Sara Habibipour, Jaimie Lim, Christian Hofmann, and Hwee Ng—all affiliated with UCLA.
