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 “signalosome” in human primary T cells. Two CAR designs were compared: a second-generation (PSCA2) and a third-generation (PSCA3) anti-PSCA CAR. Phosphorylation events triggered by CAR-mediated recognition of target cells were quantified by mass spectrometry.

OTHER RELATED OMICS DATASETS IN: GSE102823

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): T Cell, T-lymphocyte

DISEASE(S): Pancreatic Cancer

SUBMITTER: John Koomen  

LAB HEAD: Daniel Abate-Daga

PROVIDER: PXD007086 | 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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