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Specific Elimination of CD133+ Tumor Cells with Targeted Oncolytic Measles Virus.
MedLine Citation:
PMID:  23293278     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Tumor-initiating cells (TIC) are critical yet evasive targets for the development of more effective antitumoral strategies. The cell surface marker CD133 is frequently used to identify TICs of various tumor entities, including hepatocellular cancer and glioblastoma. Here, we describe oncolytic measles viruses (MV) retargeted to CD133. The viruses, termed MV-141.7 and MV-AC133, infected and selectively lysed CD133(+) tumor cells. Both viruses exerted strong antitumoral effects on human hepatocellular carcinoma growing subcutaneously or multifocally in the peritoneal cavity of nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. Notably, the CD133-targeted viruses were more effective in prolonging survival than the parental MV-NSe, which is currently assessed as oncolytic agent in clinical trials. Interestingly, target receptor overexpression or increased spreading kinetics through tumor cells were excluded as being causative for the enhanced oncolytic activity of CD133-targeted viruses. MV-141.7 was also effective in mouse models of orthotopic glioma tumor spheres and primary colon cancer. Our results indicate that CD133-targeted measles viruses selectively eliminate CD133(+) cells from tumor tissue, offering a key tool for research in tumor biology and cancer therapy. Cancer Res; 73(2); 1-10. ©2013 AACR.
Authors:
Patricia Bach; Tobias Abel; Christopher Hoffmann; Zoltan Gal; Gundula Braun; Iris Voelker; Claudia R Ball; Ian C D Johnston; Ulrich M Lauer; Christel Herold-Mende; Michael D Mühlebach; Hanno Glimm; Christian J Buchholz
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-4
Journal Detail:
Title:  Cancer research     Volume:  -     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Authors' Affiliations: Medical Biotechnology and Gene Therapy and Oncolytic Measles Viruses and Vectored Vaccines, Paul-Ehrlich-Institut, Langen; Department of Translational Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ); Division of Neurosurgical Research, Department of Neurosurgery, University of Heidelberg, Heidelberg; Miltenyi Biotec GmbH, Bergisch-Gladbach; and Department of Internal Medicine I, Medical University Hospital, Tuebingen, Germany.
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