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.