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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Production of cytokines by CD4+CAR+ T-cells in spleens

ABSTRACT: The aim of the study was to compare and contrast cytokine production by CD4+ chimeric antigen receptor + T-cells and putative myeloid derived suppressor cell populations (CD11b+Gr-1 hi and lo) in the spleens of Balb/c mice which had received a transfer of CD19 specific second-generation CAR T-cells 56 days previously following cyclophosphamide pre-conditioning. Splenocytes from four individual mice were pooled, incubated with antibodies to CD4, CD34 (CAR), CD11b, Gr-1 and sorted using flow cytometric cell sorting for CD4+CD34+, Gr-1 and the negative cell fraction. Total RNA was isolated and samples loaded in duplicate in the array. Data was normalized to global expression levels.

ORGANISM(S): Mus musculus

SUBMITTER: Dominic Rothwell

PROVIDER: E-GEOD-54696 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Production of cytokines by CD4+CAR+ T-cells in spleens

Project description:The aim of the study was to compare and contrast cytokine production by CD4+ chimeric antigen receptor + T-cells and putative myeloid derived suppressor cell populations (CD11b+Gr-1 hi and lo) in the spleens of Balb/c mice which had received a transfer of CD19 specific second-generation CAR T-cells 56 days previously following cyclophosphamide pre-conditioning.

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Expression data from chimeric antigen receptor transduced (CAR) human CD4+ T cells during expansion

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CAR T cells inhibit B cell activating phosphorylation in their targets

Project description:Adoptive cell therapy, a subset of cancer immunotherapy, is collection of therapeutic approaches which aim to redirect the immune system by reprogramming patient T-cells to target antigenic molecules differentially and specifically expressed in certain cancers. One promising immunotherapy technique is CAR T-cell therapy, where cancer cells are targeted through the expression a chimeric antigen receptor (CAR), a synthetic trans- membrane receptor that functionally compensates for the T-cell receptor (TCR) but targets a tumor associated antigen on the cancer cell surface. While CAR T-cell therapy is promising with two clinically approved second-generation CARs (Kymriah and Yescarta), few studies have investigated the mechanism of signal propagation in T-cells and no studies have investigated the potential signaling response in the target cells. To gain further insight to CAR-based signaling, we stimulated third generation CD19 CAR-expressing Jurkat T-cells by co-culture with SILAC labeled CD19HI Raji B-cells and used two phosphoenrichment strategies coupled with liquid chromatography-tandem mass spec- trometry (LC-MS/MS) to detect and analyze global phosphorylation changes in both cell populations. Analysis of the phosphopeptides originating from the CD19-CAR T cells revealed an increase in many phosphorylation events necessary for canonical TCR signaling. We also observed for the first time a significant decrease in B-cell receptor- related phosphopeptide abundance in CD19HI Raji B-cells after co-culture with CD19-targetted CAR T-cells.

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Allelic imbalance sequencing reveals that single-nucleotide polymorphisms frequently alter microRNA-directed repression

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