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@ARTICLE{Givi:304580,
author = {S. Givi and B. J. Lohnes and S. Ebrahimi and S. Riedel and
S. Khokhali and S. A. Khan and M. Keller and C. Wölfel and
H. Echchannaoui$^*$ and E. Bockamp and M. C. Andre and H.
Abken and M. Theobald$^*$ and U. F. Hartwig$^*$},
title = {{CRISPR}/{C}as9 {TCR}-{E}dited {NK}p30 {CAR} {T} {C}ells
{E}xhibit {S}uperior {A}nti-{T}umor {I}mmunity to
{B}7{H}6-{E}xpressing {L}eukemia and {M}elanoma.},
journal = {International journal of molecular sciences},
volume = {26},
number = {17},
issn = {1422-0067},
address = {Basel},
publisher = {Molecular Diversity Preservation International},
reportid = {DKFZ-2025-01903},
pages = {8235},
year = {2025},
abstract = {Chimeric antigen receptor (CAR) T-cell therapy directed to
CD19 and B-cell maturation antigen has revolutionized
treatment of B-cell leukemia and lymphoma, and multiple
myeloma. However, identifying suitable targets for acute
myeloid leukemia (AML) remains challenging due to concurrent
expression of potential target antigens on normal
hematopoietic stem cells or tissues. As the stress-induced
B7H6 molecule is rarely found on normal tissues but
expressed on many cancers including AML and melanoma, the
NKp30-ligand B7H6 emerges as a promising target for
NKp30-based CAR T therapy for these tumors. In this study,
we report a comprehensive B7H6 expression analysis on
primary AML and melanoma as well as on different tumor
cell-lines examined by RT-qPCR and flow cytometry, and
efficient anti-tumor reactivity of NKp30-CAR T cells to AML
and melanoma. To overcome limitations of autologous CAR
T-cell fitness-dependent efficacy and patient-tailored
production, we generated CRISPR/Cas9-mediated TCR-knockout
(TCRKO) NKp30-CAR T cells as an off-the-shelf approach for
CAR T therapy. Functional studies comparing NKp30-CD28 CAR
or NKp30-CD137 CAR TCR+ and TCRKO T lymphocytes revealed
superior anti-tumoral immunity of NKp30-CD28 CAR TCRKO T
cells to AML and melanoma cell lines in vitro, and effective
control of tumor burden in an NSG melanoma-xenograft mouse
model. In conclusion, these findings highlight the
therapeutic potential of NKp30 CAR TCRKO T cells for
adoptive T-cell therapy to B7H6-expressing cancers,
including melanoma and AML.},
keywords = {B7H6 expressing tumors (Other) / CAR T-cell therapy (Other)
/ NKp30-based CAR T-cell therapy (Other) / acute myeloid
leukemia (Other) / immunotherapy (Other) / melanoma (Other)},
cin = {FM01},
ddc = {540},
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:40943160},
pmc = {pmc:PMC12428420},
doi = {10.3390/ijms26178235},
url = {https://inrepo02.dkfz.de/record/304580},
}