A research team led by scientists at Albert Einstein College of Medicine announced on Mar. 13 the development of a new strategy to engineer immune cells that remain effective longer after being infused into patients to fight cancer and HIV. The findings, published in Science Advances, describe a manufacturing approach that produces longer-lasting immune cells, which provided more sustained control of human blood cancers and suppression of HIV infection in mouse models.
The significance of this work lies in addressing a major limitation of current CAR-T cell therapies: their tendency to lose potency over time, leading to disease relapse. The new method could help prolong the functional activity of these treatments and prevent recurrence.
"Our goal was to engineer therapeutic immune cells so they would not only be powerful killers but also long-lived and capable of self-renewal, to markedly extend their effectiveness after infusion into patients," said Harris Goldstein, M.D., professor at Einstein and senior author of the study. "By improving how we generate CAR-T cells, a treatment that acts as a 'living drug,' we would prolong their functional activity and prevent disease relapse after their potency wanes."
CAR-T therapy involves removing a patient's T cells, reprogramming them with genes to target cancer or virus-infected cells, then infusing them back into the patient. While initially effective, these engineered cells often lose strength over time; about half of treated cancer patients experience relapse as CAR-T cell activity diminishes. This persistence problem has also limited efforts to use CAR-T therapy against HIV.
To address this challenge, Dr. Goldstein's team developed an alternative production method using a protein scaffold called HCW9206 that links three cytokines—IL-7, IL-15, and IL-21—known for promoting T cell survival and memory. This approach generated CAR-T cells with stronger disease-fighting abilities and increased numbers of long-lived T memory stem cells compared to conventional methods.
"T memory stem cells are considered to be critical for long-term immune persistence," Goldstein said. "They can continually replenish the pool of active CAR-T cells, a crucially important attribute for their long-term success in combating both cancer and HIV infection." In mouse models simulating leukemia relapse or persistent HIV infection, only the multi-cytokine scaffold-engineered CAR-T cells mounted strong recall responses or eliminated more infected cells than standard approaches.
Goldstein said these results may help reduce blood cancer relapse rates and improve remission duration for patients receiving CAR-T therapy. For people living with HIV, he added that "immune cells with this kind of staying power may one day help maintain viral control after stopping antiretroviral therapy, a critical step toward sustained drug-free remission and, potentially, a functional cure."
