Engineering T-cells against specific viruses is becoming more efficient and feasible thanks to a research effort led by Dr. Ann Leen, associate professor at Baylor College of Medicine. Together with postdoctoral fellow Dr. Anastasia Papadopoulou and colleagues within the Center for Cell and Gene Therapy at Baylor and from Texas Children’s Hospital and Houston Methodist Hospital, Dr. Leen published the team’s methods in Science Translational Medicine. The team’s research has also been described on YouTube in a short video.
“This study translated improved manufacturing techniques developed in Dr. Leen’s laboratory to the clinic and showed that virus specific T cells produced with the new method could target new viruses and be ready for clinical use after 10 days,” said Dr. Helen Heslop, director for the Center for Cell and Gene Therapy and a co-investigator on the study, in a news release. “These advances mean that this therapy could be available for more patients to treat viral infections and provide long lasting protection.”
The focus of the study was adoptive transfer of virus-specific T-cells (VSTs). These T-cells, which in general help fight infection by recognizing viruses and eliminating infected cells, were generated through single-culture techniques using the Center for Cell and Gene Therapy’ novel manufacturing technology in order to identify five different viruses: Epstein-Barr virus, adenovirus, cytomegalovirus, BK virus, and human herpesvirus 6. These viruses were selected due to their frequent detection in immunocompromised individuals and the high rate of fatality (17-20% of cases) after infection.
The process began with isolating T-cells from bone marrow donors and ended after ten days. Following this time, eleven patients, with conditions including leukemia, lymphoma, and sickle cell disease, received allogeneic transplants of the VSTs. Eight of the patients were already actively infected with up to four of the targeted viruses, and three of the patients were trying to prevent infection.
The Center’s technology is much faster than conventional development procedures for T-cells, which can take as long as three months. It is also more effective than antiviral medications. “For example, for adenovirus the best medicine is only 50 percent effective; whereas, if you train cells to fight adenovirus directly, it’s almost 100 percent effective. And it’s more of a natural way of fighting the virus,” said Dr. Kathryn Leung, an assistant professor in the Center for Cell and Gene Therapy and another co-author.
Using engineered T-cells has also been explored at MD Anderson Cancer Center for the application of fighting fungal infections in lymphomas and leukemias. The technology used in this context is known as “Sleeping Beauty,” which was developed at University of Minnesota.