SILAC Phosphoproteomics Reveals Unique Signaling Circuits in CAR-T Cells and the Inhibition of B Cell-Activating Phosphorylation in Target Cells
Year: 2022
Type: article
Abstract: Chimeric antigen receptor (CAR) is a single-pass transmembrane receptor designed to specifically target and eliminate cancers. While CARs prove highly efficacious against B cell malignancies, the intracellular signaling events which promote CAR T cell activity remain elusive. To gain further insight into both CAR T cell signaling and the potential signaling response of cells targeted by CAR, we analyzed phosphopeptides captured by two separate phosphoenrichment strategies from third generation CD19-CAR T cells cocultured with SILAC labeled Raji B cells by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Here, we report that CD19-CAR T cells upregulated several key phosphorylation events also observed in canonical T cell receptor (TCR) signaling, while Raji B cells exhibited a significant decrease in B cell receptor-signaling related phosphorylation events in response to coculture. Our data suggest that CD19-CAR stimulation activates a mixture of unique CD19-CAR-specific signaling pathways and canonical TCR signaling, while global phosphorylation in Raji B cells is reduced after association with the CD19-CAR T cells.
Source: Journal of Proteome Research
Institutions: Brown University, Yale University
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Charles H. Hood Foundation, Rally Foundation, Yale University, Brown University, University of Arkansas for Medical Sciences, Frederick A. DeLuca Foundation, Bear Necessities Pediatric Cancer Foundation, National Institutes of Health, Yale School of Medicine, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases
OpenAlex ID: W4221032946