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Enhanced conversion of T cells into CAR T cells by modulation of the MAPK/ERK pathway

ABSTRACT: Delivery of chimeric antigen receptors (CARs) to T cells is usually mediated by lentiviral vectors (LVs), which can have broad tropism or be T-cell targeted. To better understand the molecular events during CAR T cell generation, T cell transduction with four different LVs was followed by single-cell multi-omics analysis, distinguishing between transduced T cells and T cells with vector signal but no CAR. We found that only a fraction of the T cells that had encountered vectors converted into CAR T cells. Single-cell transcriptome data revealed that interferon-stimulated genes were upregulated in non-transduced cells, whereas ERK2 phosphatases were upregulated in CAR T cells. This expression pattern was evident in CAR T cells from healthy donors and patients. The role of these genes in T cell transduction was confirmed by chemical inhibitors. These data provide molecular insights into T cell transduction with implications for improving CAR T cell generation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE273200 | GEO | 2024/12/19

REPOSITORIES: GEO

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