In the last decade, genetically engineered CAR T cells have shown tremendous therapeutic potential, especially in leukemia and lymphoma. However, when these CAR T cells are infused, the patients sometimes have severe inflammatory and neurological reactions. In fact, doctors often advise patients to live within two hours of the hospital during the thirty day recovery period after infusion. To reduce these side effects and enhance the safety of this therapy, Dr. Roy Burman is developing a method to temporarily activate CAR T cells by administering drugs. In this approach, an ON switch is attached to the CAR receptor, which targets the cancer cells, and an OFF switch is attached to the PD-1 receptor, which acts as a “brake” on T cells.
The ON switch is designed to be selectively degraded by the cell’s waste disposal system, except when treated with a drug, whereas the OFF switch only gets degraded upon drug treatment. Without the drugs, the engineered T cells will have no activity, and should prevent side effects. This form of regulation is fast, reversible, and can be personalized for different patients. Moreover, the drugs that trigger the switches are either already approved by the FDA, or in advanced clinical trials, thereby reducing the time to market. Furthermore, this approach is generalizable and could in principle be combined with any engineered cell therapy to improve its safety and effectiveness.
Projects and Grants
Regulation of CAR T Cell Activity with Clinically Approved Compounds
Dana-Farber Cancer Institute | Leukemia, Lymphoma | 2020 | Eric S. Fischer, Ph.D.