New research has discovered a reliable way to predict ICANS, a potentially life-threatening CAR T-cell therapy side effect. By analyzing cerebrospinal fluid, the team of researchers have identified specific proteins responsible for an immune response which can affect the nervous system after receiving the therapy.
Published in the journal Leukemia, the findings of the study could increase CAR-T-cell therapy safety by identifying high risk patients in advance to allow for early treatment or prevention of the condition. Despite its success in blood cancer treatment, CAR-T-cell therapy comes with serious risks including immune effector cell-associated neurotoxicity syndrome (ICANS).
During their work, the team identified 864 proteins in all the collected spinal fluid samples, which were then narrowed to the 46 which showed clear differentiation in patients who developed ICANS and those who did not. Ultimately, the team identified two proteins as the best predictors. C1RL which had elevated levels in ICANS patients, and FUCA2 which had lower levels in ICANS patients. Using these two proteins to develop a predictive test demonstrated high accuracy in distinguishing between high and low risk ICANS patients.
"If the biomarker ratio shows a patient is at high risk for ICANS, we could preemptively treat them with drugs that inhibit the complement system to lower the risk," said Dr. Yuya Kunisaki, a professor in the Department of Clinical Chemistry and Laboratory Medicine, Kyushu University Hospital. "This predictive test could therefore pave the way for a more personalized and safer approach to cancer treatment."
The team plans to continue their research with the goal of discovering key biomarkers in more easily obtainable fluids such as blood serum. "If we can identify similar biomarkers in blood, our test would become a much simpler and more accessible tool for predicting ICANS," concluded Dr. Tomoko Nomiyama, a clinical technologist at Kyushu University Hospital.