CCR5 predicts neurotoxicity in CAR-T-cell therapy

Area of Science:

• Immunology
• Neuroscience
• Oncology

Background:

• Chimeric antigen receptor T (CAR T)-cell therapy is a promising cancer treatment.
• Patients receiving CAR T-cell therapy face risks, including immune effector cell-associated neurotoxicity syndrome (ICANS).
• Identifying early biomarkers for ICANS is crucial for timely intervention.

Purpose of the Study:

• To investigate potential early biomarkers for immune effector cell-associated neurotoxicity syndrome (ICANS) in patients undergoing CAR T-cell therapy.
• To examine the expression of chemokine receptors, specifically CCR5 and CCR2, on T cells in relation to ICANS development.

Main Methods:

• Analysis of CD4+ T cell expression of CCR5 and CCR2 in patients undergoing CAR T-cell therapy.
• Correlation of chemokine receptor expression levels with the onset and presence of ICANS.
• Monitoring of receptor expression at different time points post-infusion.

Main Results:

• Upregulation of CCR5 and CCR2 expression was observed in CD4+ T cells of patients who developed ICANS.
• Increased CCR5 expression was detected as early as day one post-infusion in patients who subsequently developed ICANS.
• This early CCR5 elevation was specific to patients who eventually experienced ICANS.

Conclusions:

• CCR5 and CCR2 expression on CD4+ T cells are associated with ICANS development in CAR T-cell therapy recipients.
• Elevated CCR5 expression on day one post-infusion may serve as an early predictive biomarker for ICANS onset.
• Further research into CCR5's role could lead to improved monitoring and management of ICANS.