Irvine researchers at UC Irvine have developed a new framework that could make CAR T-cell therapy safer for patients with aggressive blood cancers. The research focuses on mitigating a potentially life-threatening complication known as immune effector cell-associated neurotoxicity syndrome, or ICANS, which can cause brain inflammation, confusion, and seizures.
CAR T-cell therapy has transformed cancer care by using a patient’s own immune cells, enhanced with chimeric antigen receptors, to recognize and destroy cancer cells when reintroduced into the body. While effective against many blood cancers, the intense immune response generated by this treatment can sometimes lead to ICANS.
Currently, clinicians primarily use corticosteroids to manage ICANS. Although these steroids can be effective for many patients, they can also produce significant side effects and may not address the core biological mechanisms driving the syndrome. The UC Irvine team's study, published in *Frontiers in Pharmacology*, highlights mitochondrial dysfunction as a key contributor to ICANS.
Instead of developing entirely new medications, the researchers propose evaluating existing drugs that already have established safety profiles. This approach could potentially accelerate the path toward clinical testing and improve outcomes for cancer patients by providing safer treatment strategies.
Atena Zahedi, assistant professor of clinical pharmacy practice in UC Irvine’s School of Pharmacy & Pharmaceutical Sciences and lead author of the study, stated that their work points to mitochondrial dysfunction as a promising therapeutic target for the neurological complications of CAR T-cell therapy. She noted that identifying existing drugs for repurposing could accelerate the development of safer treatment strategies.
The interdisciplinary team focused on mitochondria, which are cellular structures responsible for producing energy and regulating immune function. Their research indicates that when mitochondria become dysfunctional, they may amplify the inflammatory response that contributes to neurological injury following CAR T-cell therapy.
Co-author Shawn Griffin, an oncology pharmacist and associate clinical professor of clinical pharmacy practice at UC Irvine, emphasized the opportunity in identifying existing drugs for repurposing. He explained that because many of these medications already have established safety profiles, they could move into clinical evaluation more quickly than new drug development. The goal is to accelerate the discovery of safer treatment options that protect patients while preserving the lifesaving benefits of CAR T-cell therapy.
For co-author Onwodi Ifejeokwu, this research holds personal significance. She lost a family member to B cell lymphoma in 2021 and witnessed the devastating effects of cancer treatment on the brain, which fueled her passion for neuro-immuno-oncology research. She works alongside her mentors, Zahedi, Dean, and Griffin, to enhance the quality of life for cancer patients.
Beyond identifying potential drug repurposing, the study also provides a roadmap for translating these findings into future clinical research. Senior author Dr. Erin Dean, a medical oncologist at UC Irvine’s Chao Family Comprehensive Cancer Center, is currently leading related clinical research efforts aimed at evaluating new approaches to improve patient care.
