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@ARTICLE{Peschke:277703,
author = {J. C. Peschke and R. Bergmann and M. Mehnert and K. E.
Gonzalez Soto and L. R. Loureiro and N. Mitwasi and A.
Kegler and H. Altmann$^*$ and M. Wobus$^*$ and D. Máthé
and K. Szigeti and A. Feldmann$^*$ and M. Bornhäuser and M.
Bachmann$^*$ and F. Fasslrinner and C. Arndt},
title = {{FLT}3-directed {U}ni{CAR} {T}-cell therapy of acute
myeloid leukaemia.},
journal = {British journal of haematology},
volume = {202},
number = {6},
issn = {0007-1048},
address = {Oxford [u.a.]},
publisher = {Wiley-Blackwell},
reportid = {DKFZ-2023-01420},
pages = {1137-1150},
year = {2023},
note = {2023 Sep;202(6):1137-1150},
abstract = {Adaptor chimeric antigen receptor (CAR) T-cell therapy
offers solutions for improved safety and antigen escape,
which represent main obstacles for the clinical translation
of CAR T-cell therapy in myeloid malignancies. The adaptor
CAR T-cell platform 'UniCAR' is currently under early
clinical investigation. Recently, the first proof of concept
of a well-tolerated, rapidly switchable, CD123-directed
UniCAR T-cell product treating patients with acute myeloid
leukaemia (AML) was reported. Relapsed and refractory AML is
prone to high plasticity under therapy pressure targeting
one single tumour antigen. Thus, targeting of multiple
tumour antigens seems to be required to achieve durable
anti-tumour responses, underlining the need to further
design alternative AML-specific target modules (TM) for the
UniCAR platform. We here present the preclinical development
of a novel FMS-like tyrosine kinase 3 (FLT3)-directed UniCAR
T-cell therapy, which is highly effective for in vitro
killing of both AML cell lines and primary AML samples.
Furthermore, we show in vivo functionality in a murine
xenograft model. PET analyses further demonstrate a short
serum half-life of FLT3 TMs, which will enable a rapid
on/off switch of UniCAR T cells. Overall, the presented
preclinical data encourage the further development and
clinical translation of FLT3-specific UniCAR T cells for the
therapy of AML.},
keywords = {CAR T cells (Other) / CD135 (Other) / FLT3 (Other) / UniCAR
(Other) / acute myeloid leukaemia (Other)},
cin = {DD01},
ddc = {610},
cid = {I:(DE-He78)DD01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37460273},
doi = {10.1111/bjh.18971},
url = {https://inrepo02.dkfz.de/record/277703},
}