Document Detail


RD114-pseudotyped retroviral vectors kill cancer cells by syncytium formation and enhance the cytotoxic effect of the TK/GCV gene therapy strategy.
MedLine Citation:
PMID:  15619289     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Wild-type RD114 virus is capable of generating syncytia during its replication, and it is believed that cell-free viruses direct the fusion of neighboring cells. The RD114 envelope (Env) that mediates this fusion event is now widely used to pseudotype retroviral and lentiviral vectors in gene therapy. Indeed, vectors pseudotyped with RD114 Env are very efficient to transfer genes into human hematopoietic cells, and they are resistant to human complement inactivation. In this study, we have tested the potential of RD114-pseudotyped vectors produced from the FLYRD18 packaging cell line to induce syncytia. METHODS: RD114-pseudotyped vectors produced from the FLYRD18 packaging cells were added on tumor cell lines, and the formation of syncytia was assessed by microscopy after cell fixation and methylene blue staining. The kinetics of syncytium formation was analyzed by time-lapse microscopy. Finally, the cytotoxic effect of RD114-pseudotyped vectors was measured by the MTT assay on tumor cells, and in combination with the TK/GCV strategy. RESULTS: We have found that these vectors were able to mediate cell-to-cell fusion of human tumor cell lines. A few hours after addition of the vector, cells started to aggregate to form syncytia that eventually evolved toward cell death 48 h postinfection. RD114-pseudotyped vectors were very efficient at killing human cancer cells, and they were also able to enhance dramatically the cytotoxic effect of the TK/GCV strategy. CONCLUSIONS: These findings indicate that RD114-pseudotyped vectors used alone, or in combination with a suicide gene therapy approach, have great potential for the treatment of cancer.
Authors:
E Germain; V-G Roullin; J Qiao; P O de Campos Lima; M Caruso
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The journal of gene medicine     Volume:  7     ISSN:  1099-498X     ISO Abbreviation:  J Gene Med     Publication Date:  2005 Apr 
Date Detail:
Created Date:  2005-04-11     Completed Date:  2005-09-26     Revised Date:  2006-04-21    
Medline Journal Info:
Nlm Unique ID:  9815764     Medline TA:  J Gene Med     Country:  England    
Other Details:
Languages:  eng     Pagination:  389-97     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2004 John Wiley & Sons, Ltd.
Affiliation:
Le Centre de Recherche en Cancérologie de l'Université Laval, L'Hôtel-Dieu de Québec, Centre Hospitalier Universitaire de Québec, Québec G1R 2J6, Canada.
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MeSH Terms
Descriptor/Qualifier:
Bystander Effect
Cell Line, Tumor
Cell Proliferation
Ganciclovir / therapeutic use*
Gene Therapy*
Genetic Vectors*
Giant Cells / pathology*
Humans
Neoplasms / enzymology,  pathology*
Retroviridae / genetics*
Thymidine Kinase / genetics*
Chemical
Reg. No./Substance:
82410-32-0/Ganciclovir; EC 2.7.1.21/Thymidine Kinase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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