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@ARTICLE{Kaczorowski:128859,
author = {A. Kaczorowski and K. Hammer$^*$ and L. Liu and S.
Villhauer and C. Nwaeburu and P. Fan and Z. Zhao and J.
Gladkich and W. Groß and D. Nettelbeck$^*$ and I. Herr},
title = {{D}elivery of improved oncolytic adenoviruses by
mesenchymal stromal cells for elimination of tumorigenic
pancreatic cancer cells.},
journal = {OncoTarget},
volume = {7},
number = {8},
issn = {1949-2553},
address = {[S.l.]},
publisher = {Impact Journals LLC},
reportid = {DKFZ-2017-04872},
pages = {9046 - 9059},
year = {2016},
abstract = {Pancreatic ductal adenocarcinoma (PDA) is one of the most
aggressive malignancies and has poor therapeutic options. We
evaluated improved oncolytic adenoviruses (OAds), in which
the adenoviral gene E1B19K was deleted or a TRAIL transgene
was inserted. Bone marrow mesenchymal stromal cells (MSCs)
served as carriers for protected and tumor-specific virus
transfers. The infection competence, tumor migration, and
oncolysis were measured in cancer stem cell (CSC) models of
primary and established tumor cells and in tumor xenografts.
All OAds infected and lysed CSCs and prevented colony
formation. MSCs migrated into PDA spheroids without impaired
homing capacity. Xenotransplantation of non-infected PDA
cells mixed with infected tumor cells strongly reduced the
tumor volume and the expression of the proliferation marker
Ki67 along with a necrotic morphology. Adenoviral capsid
protein was detected in tumor xenograft tissue after
intravenous injection of infected MSCs, but not in normal
tissue, implying tumor-specific migration. Likewise, direct
in vivo treatment correlated with a strongly reduced tumor
volume, lower expression of Ki67 and CD24, and enhanced
activity of caspase 3. These data demonstrate that the
improved OAds induced efficient oncolysis with the OAd-TRAIL
as most promising candidate for future clinical
application.},
keywords = {Adaptor Proteins, Signal Transducing (NLM Chemicals) /
Antigens, CD24 (NLM Chemicals) / CD24 protein, human (NLM
Chemicals) / Capsid Proteins (NLM Chemicals) / Ki-67 Antigen
(NLM Chemicals) / Caspase 3 (NLM Chemicals)},
cin = {F110},
ddc = {610},
cid = {I:(DE-He78)F110-20160331},
pnm = {316 - Infections and cancer (POF3-316)},
pid = {G:(DE-HGF)POF3-316},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:26824985},
pmc = {pmc:PMC4891025},
doi = {10.18632/oncotarget.7031},
url = {https://inrepo02.dkfz.de/record/128859},
}