Marker genes for predicting cytokine release syndrome in vitro before CAR T cell infusion

Abstract

Cytokine release syndrome (CRS) and neurotoxicity are common adverse events of the Chimeric antigen receptor (CAR) T cell therapy. Assessing the cytotoxicity associated biomarkers would be essential for therapy design to avoid developing severe toxicities. In this study, we re-analyzed previously published RNAseq results of CAR T cells before infusion and combined it with the clinical response post infusion. We observed that CAR T cells from patients who developed severe CRS displayed a higher expression of TCL6, HPCAL4, CCDC144B, and SIRPG, but lower levels of IL2, IL21, and HSPA1B when stimulated with anti-CAR19 idiotypic antibody in vitro. Interestingly, the upregulated gene SIRPG is positively correlated with CRS severity. In addition, without stimulation, CAR T cells from CRS group showed a higher levels of IFNAR1, IL7R, ZNF69, and USP32P1 but lower levels of CCL3, IL4, IL17A, IL23R, IL13, CD70, and IFNGR2. These results provided insights to evaluate the adverse events of CAR T products before treatments, which could be beneficial for designing therapy plans.