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@ARTICLE{Adabi:298908,
author = {E. Adabi and F. T. Charitidis and F. B. Thalheimer and M.
Guaza-Lasheras and C. Clarke and C. J. Buchholz$^*$},
title = {{E}nhanced conversion of {T} cells into {CAR} {T} cells by
modulation of the {MAPK}/{ERK} pathway.},
journal = {Cell reports / Medicine},
volume = {6},
number = {2},
issn = {2666-3791},
address = {Cambridge, MA},
publisher = {Cell Press},
reportid = {DKFZ-2025-00347},
pages = {101970},
year = {2025},
note = {2025 Feb 18;6(2):101970},
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 is followed by
single-cell multi-omics analysis, distinguishing between
transduced T cells and T cells with vector signal but no
CAR. We find that only a fraction of the T cells that
encounter vectors convert into CAR T cells. Single-cell
transcriptome data reveal that interferon-stimulated genes
are upregulated in non-transduced cells, whereas
extracellular signal-regulated kinase (ERK)2 phosphatases
are upregulated in CAR T cells. This expression pattern is
evident in CAR T cells from healthy donors and patients. The
role of the mitogen-activated protein kinase (MAPK)/ERK
pathway in CAR T cell generation is confirmed by chemical
inhibitors. These data provide molecular insights into T
cell transduction with implications for improving CAR T cell
generation.},
keywords = {CAR T cells, lentiviral vector, adeno-associated vector,
interferon-stimulated genes, MAPK/ERK pathway, ERK2
inhibitors (Other)},
cin = {FM01},
ddc = {610},
cid = {I:(DE-He78)FM01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39938523},
doi = {10.1016/j.xcrm.2025.101970},
url = {https://inrepo02.dkfz.de/record/298908},
}