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• W2943291219 endingPage "602" @default.
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• W2943291219 abstract "Hypoxia is a major characteristic of the solid tumor microenvironment. To understand how chimeric antigen receptor-T cells (CAR-T cells) function in hypoxic conditions, we characterized CD19-specific and BCMA-specific human CAR-T cells generated in atmospheric (18% oxygen) and hypoxic (1% oxygen) culture for expansion, differentiation status, and CD4:CD8 ratio. CAR-T cells expanded to a much lower extent in 1% oxygen than in 18% oxygen. Hypoxic CAR-T cells also had a less differentiated phenotype and a higher CD4:CD8 ratio than atmospheric CAR-T cells. CAR-T cells were then added to antigen-positive and antigen-negative tumor cell lines at the same or lower oxygen level and characterized for cytotoxicity, cytokine and granzyme B secretion, and PD-1 upregulation. Atmospheric and hypoxic CAR-T cells exhibited comparable cytolytic activity and PD-1 upregulation; however, cytokine production and granzyme B release were greatly decreased in 1% oxygen, even when the CAR-T cells were generated in atmospheric culture. Together, these data show that at solid tumor oxygen levels, CAR-T cells are impaired in expansion, differentiation and cytokine production. These effects may contribute to the inability of CAR-T cells to eradicate solid tumors seen in many patients." @default.
• W2943291219 created "2019-05-09" @default.
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• W2943291219 date "2019-04-30" @default.
• W2943291219 modified "2023-10-16" @default.
• W2943291219 title "Hypoxia Selectively Impairs CAR-T Cells In Vitro" @default.
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• W2943291219 doi "https://doi.org/10.3390/cancers11050602" @default.
• W2943291219 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6562712" @default.
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• W2943291219 hasPublicationYear "2019" @default.
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