Neural stem cell-based cell carriers enhance therapeutic efficacy of an oncolytic adenovirus in an orthotopic mouse model of human glioblastoma.

作者: Atique U Ahmed , Bart Thaci , Nikita G Alexiades , Yu Han , Shuo Qian

DOI: 10.1038/MT.2011.100

关键词:

摘要: The potential utility of oncolytic adenoviruses as anticancer agents is significantly hampered by the inability currently available viral vectors to effectively target micrometastatic tumor burden. Neural stem cells (NSCs) have ability function cell carriers for targeted delivery an adenovirus because their inherent tumor-tropic migratory ability. We previously reported that in vivo CRAd-S-pk7, a glioma-restricted adenovirus, can enhance survival animals with experimental glioma. In this study, we show intratumoral NSCs loaded CRAD-S-pk7 orthotopic xenograft model human glioma able not only inhibit growth but more importantly increase median ~50% versus treated CRAd-S-pk7 alone (P = 0.0007). also report virus infection upregulates different chemoattractant receptors and enhances capacity both vitro vivo. Our data further suggest NSC-based improve clinical efficacy antiglioma virotherapy protecting therapeutic from host immune system, amplifying payload selectively at sites.

参考文章(32)
Sara Benedetti, Barbara Pirola, Bianca Pollo, Lorenzo Magrassi, Maria Grazia Bruzzone, Dorotea Rigamonti, Rossella Galli, Silvia Selleri, Francesco Di Meco, Claudio De Fraja, Angelo Vescovi, Elena Cattaneo, Gaetano Finocchiaro, Gene therapy of experimental brain tumors using neural progenitor cells Nature Medicine. ,vol. 6, pp. 447- 450 ,(2000) , 10.1038/74710
Mariana Puntel, Kurt M. Kroeger, Nicholas S.R. Sanderson, Clare E. Thomas, Maria G. Castro, Pedro R. Lowenstein, Gene transfer into rat brain using adenoviral vectors. Current protocols in protein science. ,vol. 50, ,(2000) , 10.1002/0471142301.NS0424S50
Ofira Einstein, Tamir Ben-Hur, The changing face of neural stem cell therapy in neurologic diseases. JAMA Neurology. ,vol. 65, pp. 452- 456 ,(2008) , 10.1001/ARCHNEUR.65.4.452
M A Tyler, I V Ulasov, A M Sonabend, S Nandi, Y Han, S Marler, J Roth, M S Lesniak, Neural stem cells target intracranial glioma to deliver an oncolytic adenovirus in vivo Gene Therapy. ,vol. 16, pp. 262- 278 ,(2009) , 10.1038/GT.2008.165
K. S. Aboody, A. Brown, N. G. Rainov, K. A. Bower, S. Liu, W. Yang, J. E. Small, U. Herrlinger, V. Ourednik, P. McL. Black, X. O. Breakefield, E. Y. Snyder, Neural stem cells display extensive tropism for pathology in adult brain: evidence from intracranial gliomas. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 97, pp. 12846- 12851 ,(2000) , 10.1073/PNAS.97.23.12846
Stefano Pluchino, Lucia Zanotti, Barbara Rossi, Elena Brambilla, Linda Ottoboni, Giuliana Salani, Marianna Martinello, Alessandro Cattalini, Alessandra Bergami, Roberto Furlan, Giancarlo Comi, Gabriela Constantin, Gianvito Martino, Neurosphere-derived multipotent precursors promote neuroprotection by an immunomodulatory mechanism. Nature. ,vol. 436, pp. 266- 271 ,(2005) , 10.1038/NATURE03889
Thomas L. Sims, J. Blair Hamner, Rebecca A. Bush, Peter E. Fischer, Seung U. Kim, Karen S. Aboody, Beth McCarville, Mary K. Danks, Andrew M. Davidoff, Neural progenitor cell–mediated delivery of osteoprotegerin limits disease progression in a preclinical model of neuroblastoma bone metastasis Journal of Pediatric Surgery. ,vol. 44, pp. 204- 211 ,(2009) , 10.1016/J.JPEDSURG.2008.10.041
Ilya V. Ulasov, Zeng B. Zhu, Matthew A. Tyler, Yu Han, Angel A. Rivera, Andrey Khramtsov, David T. Curiel, Maciej S. Lesniak, Survivin-driven and fiber-modified oncolytic adenovirus exhibits potent antitumor activity in established intracranial glioma. Human Gene Therapy. ,vol. 18, pp. 589- 602 ,(2007) , 10.1089/HUM.2007.002
D. L. Montgomery, Astrocytes: Form, Functions, and Roles in Disease Veterinary Pathology. ,vol. 31, pp. 145- 167 ,(1994) , 10.1177/030098589403100201
Ramachandran Ramalingam, Stefan Worgall, Shahin Rafii, Ronald G. Crystal, Downregulation of CXCR4 Gene Expression in Primary Human Endothelial Cells Following Infection with E1−E4+ Adenovirus Gene Transfer Vectors Molecular Therapy. ,vol. 2, pp. 381- 386 ,(2000) , 10.1006/MTHE.2000.0131