Irvine, Calif. – Researchers at UC Irvine have developed a new framework aimed at making CAR T-cell therapy safer for cancer patients. The work focuses on preventing immune effector cell-associated neurotoxicity syndrome (ICANS), a serious neurological complication that can arise from the powerful immunotherapy. ICANS can manifest as brain inflammation, confusion, and seizures, affecting patients undergoing treatment for aggressive blood cancers.
Published in *Frontiers in Pharmacology*, the study identifies mitochondrial dysfunction as a key contributor to ICANS. Rather than advocating for the development of entirely new medications, the UC Irvine team proposes evaluating existing drugs that already possess established safety profiles. This strategy could significantly accelerate the path toward clinical testing and improve outcomes for patients.
Atena Zahedi, an assistant professor of clinical pharmacy practice in UC Irvine’s School of Pharmacy & Pharmaceutical Sciences and lead author, stated that the work "points to mitochondrial dysfunction as a promising therapeutic target" for managing this severe complication. She emphasized that identifying existing drugs could hasten the creation of safer treatment strategies while preserving the life-saving benefits of CAR T-cell therapies.
CAR T-cell therapy involves extracting a patient’s immune cells, enhancing them with chimeric antigen receptors, and then reintroducing them to target and destroy cancer. While this treatment has yielded remarkable results for many blood cancers, the intense immune response it generates can sometimes trigger ICANS, impacting the brain and nervous system. Current clinical practice primarily relies on corticosteroids to control inflammation, but these medications can have significant side effects and may not address the underlying biological mechanisms driving ICANS.
The interdisciplinary UC Irvine team concentrated on mitochondria, structures within cells responsible for energy production and immune function. Their research suggests 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, highlighted the advantage of identifying existing medications. He explained that because many of these drugs already have established safety profiles, they could potentially move into clinical evaluation more quickly than newly developed ones. The overarching objective is to protect patients while maintaining the therapy’s effectiveness.
For co-author Onwodi Ifejeokwu, the research is personal. She lost a family member to B cell lymphoma in 2021 and witnessed firsthand the devastating brain-related complications of cancer treatment. This experience fueled her dedication to neuro-immuno-oncology research alongside her mentors Zahedi, Dean, and Griffin.
The study also provides a roadmap for translating these findings into future clinical research. Dr. Erin Dean, a medical oncologist at UC Irvine’s Chao Family Comprehensive Cancer Center and senior author, is leading related clinical research efforts aimed at evaluating new approaches to enhance patient care.
