Proteomics,Multiomics

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An immunoproteomic approach to characterize the CAR interactome and signalosome


ABSTRACT: Adoptive transfer of chimeric antigen receptor (CAR)-T cells is expected to become the first line of treatment for multiple malignancies, following the enormous success of anti-CD19 therapies. However, their mechanism of action is not fully understood, and clear guidelines for the design of safe and efficient receptors are missing. We hereby describe a systematic analysis of the CAR “interactome” in human primary T cells, which allowed us to identify molecular traits that influence CAR-T cell efficacy. Interactome analysis was based on immunoprecipitation of CARs followed by protein identification by mass spectrometry.

OTHER RELATED OMICS DATASETS IN: GSE102823

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): T Cell, Cell Culture, T-lymphocyte

DISEASE(S): Cancer

SUBMITTER: John Koomen  

LAB HEAD: Daniel Abate-Daga

PROVIDER: PXD007085 | Pride | 2019-11-07

REPOSITORIES: Pride

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Publications


Adoptive transfer of T cells that express a chimeric antigen receptor (CAR) is an approved immunotherapy that may be curative for some hematological cancers. To better understand the therapeutic mechanism of action, we systematically analyzed CAR signaling in human primary T cells by mass spectrometry. When we compared the interactomes and the signaling pathways activated by distinct CAR-T cells that shared the same antigen-binding domain but differed in their intracellular domains and their in  ...[more]

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