Longitudinal Serum Proteomics Characterization of CD19-CAR-T Cell Therapy for B-Cell Malignancies

Chimeric antigen receptor (CAR)-modified T cells have demonstrated remarkable efficacy in treating B-cell leukemia. However, treated patients may potentially develop side effects, such as cytokine release syndrome (CRS), the mechanisms of which remain unclear. Here, we collected 43 serum samples from eight patients with B-cell acute lymphoblastic leukemia (B-ALL) before and five time points after CD19-specific CAR-T cell treatment. Using TMTpro 16-plex-based quantitative proteomics, we quantified 1151 proteins and profiled the longitudinal proteomes analysis of each patient. Seven days after therapy, we found the most dysregulated inflammatory proteins. Lipid metabolism proteins, including APOA1, decreased after therapy, reached their minimum after 7 days, and then gradually recovered. Hence, APOA1 has been selected as a potential biomarker of the CRS disease progression. Furthermore, we identified CD163 as a potential biomarker of CRS severity. These two biomarkers were successfully validated using targeted proteomics in an independent cohort. Our study provides new insights into CAR-T cell therapy-induced CRS. The biomarkers we identified may help develop targeted drugs and monitoring strategies.