Investigating the role of IFNγ in the development of cytokine release syndrome and chimeric antigen receptor (CAR)T cell efficacy
i4Kids Pilot Grant FY27
Project Period: September 1, 2026 - February 28, 2028
Award Amount: $50,000
Erica Braverman, MD
Assistant Professor
Department of Pediatrics, Division of Hematology/Oncology
University of Pittsburgh School of Medicine
Immunotherapies are medical treatments in which a patient’s own immune system is harnessed in the fight against their disease. One type of immunotherapy, called chimeric antigen receptor (CAR) T cells, has made a significant impact on our ability to cure children with a type of cancer called acute lymphoblastic leukemia (ALL). However, CART cells have not seen the same success against other cancers, which means we are still working to understand how to make CART cells better. Importantly, CART cells are also being used outside of cancer to treat autoimmune diseases, suggesting that understanding how to make these CART cells as efficacious as possible holds the promise of curing many diseases. At the same time, we also know that along with a therapy as powerful as CART cells comes significant side effects, the most common of which is called cytokine release syndrome, or CRS. Patients with CRS become very ill and often require hospitalization in the ICU. Understanding exactly what causes CRS could significantly improve our ability to predict those patients most at risk and better treat those patients who develop symptoms. This is particularly important for children as they are more likely to develop severe CRS than adults. In our lab, we have uncovered specific cytokines, which are proteins that allow cells to talk to each other, that interact to play a significant role in both the development of CRS and in the ability of CART cells to fight against different cancers. These findings present us with the opportunity to work towards both a better understanding of how CRS develops while also identifying ways to make CART cells function better. Our ultimate goal is to create a more powerful and effective CART therapy with fewer side effects to better treat and cure children.
