Document Detail


Electroporation gene therapy preclinical and clinical trials for melanoma.
MedLine Citation:
PMID:  20557286     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In vivo electroporation (EP) is a versatile delivery method for gene transfer which can be applied to any accessible tissue. Delivery of plasmid DNA encoding therapeutic genes or cDNAs with in vivo EP has been tested extensively in preclinical melanoma models. Direct delivery to the tumor has been shown to generate a direct antitumor effect. Delivery to alternative sites may generate additional therapeutic options, for example the production of cancer vaccines, the reduction of tumor angiogenesis, or the induction of tumor cell apoptosis. Several of the preclinical therapies tested have a demonstrated therapeutic effect against melanomas. Two immunotherapies have advanced to melanoma clinical trials. Delivery of a plasmid DNA encoding interleukin-12 (IL-12) or interleukin-2 (IL-2) using electroporation was demonstrated to be a safe with no grade 3 or 4 toxicities reported. Delivery of IL-12 with electroporation resulted in significant necrosis of melanoma cells in the majority of treated tumors and significant lymphocytic infiltrate in biopsies from patients in several cohorts. In addition, clinical evidence of responses in untreated lesions suggested the induction of a systemic response following therapy. This review discusses preclinically tested electroporation gene therapies for melanoma with clinical potential and the conversion of these therapies to clinical trials.
Authors:
Loree C Heller; Richard Heller
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Current gene therapy     Volume:  10     ISSN:  1875-5631     ISO Abbreviation:  Curr Gene Ther     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-19     Completed Date:  2010-12-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101125446     Medline TA:  Curr Gene Ther     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  312-7     Citation Subset:  IM    
Affiliation:
Frank Reidy Research Center for Bioelectrics, Old Dominion University, 4211 Monarch Way, Suite 300, Norfolk, VA 23508, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Clinical Trials as Topic
Electrochemotherapy / methods*
Female
Gene Therapy / adverse effects,  methods*
Gene Transfer Techniques / adverse effects
Humans
Interleukin-12 / adverse effects,  genetics,  therapeutic use
Interleukin-2 / adverse effects,  genetics,  therapeutic use
Melanoma / therapy*
Mice
Neovascularization, Pathologic / therapy
Plasmids / adverse effects,  therapeutic use
Skin Neoplasms / therapy*
Chemical
Reg. No./Substance:
0/Interleukin-2; 187348-17-0/Interleukin-12

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


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