TY  - JOUR
AU  - Peschke, J. C.
AU  - Bergmann, R.
AU  - Mehnert, M.
AU  - Gonzalez Soto, K. E.
AU  - Loureiro, L. R.
AU  - Mitwasi, N.
AU  - Kegler, A.
AU  - Altmann, H.
AU  - Wobus, M.
AU  - Máthé, D.
AU  - Szigeti, K.
AU  - Feldmann, A.
AU  - Bornhäuser, M.
AU  - Bachmann, Marion
AU  - Fasslrinner, F.
AU  - Arndt, C.
TI  - FLT3-directed UniCAR T-cell therapy of acute myeloid leukaemia.
JO  - British journal of haematology
VL  - 202
IS  - 6
SN  - 0007-1048
CY  - Oxford [u.a.]
PB  - Wiley-Blackwell
M1  - DKFZ-2023-01420
SP  - 1137-1150
PY  - 2023
N1  - 2023 Sep;202(6):1137-1150
AB  - 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.
KW  - CAR T cells (Other)
KW  - CD135 (Other)
KW  - FLT3 (Other)
KW  - UniCAR (Other)
KW  - acute myeloid leukaemia (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:37460273
DO  - DOI:10.1111/bjh.18971
UR  - https://inrepo02.dkfz.de/record/277703
ER  -