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Genome-wide analysis of the effect of long-term cryopreservation on peripheral blood mononuclear cells

ABSTRACT: Analysis of effect of long-term cryopreservation on peripheral blood mononuclear cells at gene expression level. The hypothesis tested in the present study was that long-term cryopreservation has an influence on the transcriptome profile of peripheral blood mononuclear cells. Results indicated remarkable changes in expression patterns upon cryopreservation of PBMCs, with decreasing signal intensities over time.

ORGANISM(S): Homo sapiens

PROVIDER: GSE24755 | GEO | 2011/07/22

SECONDARY ACCESSION(S): PRJNA133393

REPOSITORIES: GEO

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Genome-wide analysis of the effect of long-term cryopreservation on peripheral blood mononuclear cells

Project description:Analysis of effect of long-term cryopreservation on peripheral blood mononuclear cells at gene expression level. The hypothesis tested in the present study was that long-term cryopreservation has an influence on the transcriptome profile of peripheral blood mononuclear cells. Results indicated remarkable changes in expression patterns upon cryopreservation of PBMCs, with decreasing signal intensities over time. Total RNA obtained from isolated peripheral blood mononuclear cells of melanoma patients cryopreserved in liqiud nitrogen from 20 to 60 months.

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Genome-wide analysis of the effect of cryopreservation on peripheral blood mononuclear cells

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Genome-wide analysis of the effect of cryopreservation on peripheral blood mononuclear cells

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Homo sapiens

Project description:Genome-wide analysis of the effect of long-term cryopreservation on peripheral blood mononuclear cells

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Effect of Cryopreservation on Autologous Chimeric Antigen Receptor T Cell Characteristics

Project description:As clinical applications for chimeric antigen receptor T cell (CART) therapy extend beyond early phase trials, commercial manufacture incorporating preservation steps becomes a logistical necessity. The effect of cryopreservation on CART characteristics is unclear. We retrospectively evaluated the effect of cryopreservation on product release criteria and in vivo characteristics in 158 autologous CART products from 6 single-center clinical trials. Further, from 3 healthy donor manufacturing runs, we prospectively identified differentially expressed cell surface markers and gene signatures among fresh versus cryopreserved CARTs. Within 2 days of culture initiation, cell viability of the starting fraction (peripheral blood mononuclear cells [PBMNCs]) decreased significantly in the cryo-thawed arm compared to the fresh arm. Despite this, PBMNC cryopreservation did not affect final CART fold expansion, transduction efficiency, CD3%, or CD4:CD8 ratios. In vivo CART persistence and clinical responses did not differ among fresh and cryopreserved final products. In healthy donors, compared to fresh CARTs, early apoptotic cell-surface markers were significantly elevated in cryo-thawed CARTs. Cryo-thawed CARTs also demonstrated significantly elevated expression of mitochondrial dysfunction, apoptosis signaling, and cell cycle damage pathways. Cryopreservation during CART manufacture is a viable strategy, based on standard product release parameters. The clinical impact of cryopreservationrelated subtle micro-cellular damage needs further study

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