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@ARTICLE{Theruvath:154632,
author = {J. Theruvath and E. Sotillo and C. W. Mount and C. M. Graef
and A. Delaidelli and S. Heitzeneder and L. Labanieh and S.
Dhingra and A. Leruste and R. G. Majzner and P. Xu and S.
Mueller and D. W. Yecies and M. A. Finetti and D. Williamson
and P. D. Johann$^*$ and M. Kool$^*$ and S. Pfister$^*$ and
M. Hasselblatt and M. C. Frühwald and O. Delattre and D.
Surdez and F. Bourdeaut and S. Puget and S. Zaidi and S. S.
Mitra and S. Cheshier and P. H. Sorensen and M. Monje and C.
L. Mackall},
title = {{L}ocoregionally administered {B}7-{H}3-targeted {CAR} {T}
cells for treatment of atypical teratoid/rhabdoid tumors.},
journal = {Nature medicine},
volume = {26},
number = {5},
issn = {1546-170X},
address = {New York, NY},
publisher = {Nature America Inc.},
reportid = {DKFZ-2020-00900},
pages = {712-719},
year = {2020},
note = {2020 May;26(5):712-719},
abstract = {Atypical teratoid/rhabdoid tumors (ATRTs) typically arise
in the central nervous system (CNS) of children under 3
years of age. Despite intensive multimodal therapy (surgery,
chemotherapy and, if age permits, radiotherapy), median
survival is 17 months1,2. We show that ATRTs robustly
express B7-H3/CD276 that does not result from the
inactivating mutations in SMARCB1 (refs. 3,4), which drive
oncogenesis in ATRT, but requires residual SWItch/Sucrose
Non-Fermentable (SWI/SNF) activity mediated by BRG1/SMARCA4.
Consistent with the embryonic origin of ATRT5,6, B7-H3 is
highly expressed on the prenatal, but not postnatal, brain.
B7-H3.BB.z-chimeric antigen receptor (CAR) T cells
administered intracerebroventricularly or intratumorally
mediate potent antitumor effects against cerebral ATRT
xenografts in mice, with faster kinetics, greater potency
and reduced systemic levels of inflammatory cytokines
compared to CAR T cells administered intravenously. CAR T
cells administered ICV also traffic from the CNS into the
periphery; following clearance of ATRT xenografts,
B7-H3.BB.z-CAR T cells administered
intracerebroventricularly or intravenously mediate
antigen-specific protection from tumor rechallenge, both in
the brain and periphery. These results identify B7-H3 as a
compelling therapeutic target for this largely incurable
pediatric tumor and demonstrate important advantages of
locoregional compared to systemic delivery of CAR T cells
for the treatment of CNS malignancies.},
cin = {B062 / HD01},
ddc = {610},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32341579},
doi = {10.1038/s41591-020-0821-8},
url = {https://inrepo02.dkfz.de/record/154632},
}