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Mouse Mammary Tumor Virus Promoter-Containing Retroviral Promoter Conversion Vectors for Gene-Directed Enzyme Prodrug Therapy are Functional In Vitro and In Vivo
Joint Authors
Ruttkowski, Bärbel
Schwab, Sonja
Peterbauer, Thomas
Günzburg, Walter H.
Hohenadl, Christine
Salmons, Brian
Klein, Reinhard
Source
Issue
Vol. 2008, Issue 2008 (31 Dec. 2008), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2008-01-20
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
Gene directed-enzyme prodrug therapy (GDEPT) is an approach for sensitization of tumor cells to an enzymatically activated, otherwise nontoxic, prodrug.
Cytochrome P450 2B1 (CYP2B1) metabolizes the prodrugs cyclophosphamide (CPA) and ifosfamide (IFA) to produce the cytotoxic substances phosphoramide mustard and isophosphoramide mustard as well as the byproduct acrolein.
We have constructed a retroviral promoter conversion (ProCon) vector for breast cancer GDEPT.
The vector allows expression of CYP2B1 from the mouse mammary tumor virus (MMTV) promoter known to be active in the mammary glands of transgenic animals.
It is anticipated to be used for the generation of encapsulated viral vector producing cells which, when placed inside or close to a tumor, will act as suppliers of the therapeutic CYP2B1 protein as well as of the therapeutic vector itself.
The generated vector was effectively packaged by virus producing cells and allowed the production of high levels of enzymatically active CYP2B1 in infected cells which sensitized them to killing upon treatment with both IFA and CPA.
Determination of the respective IC50 values demonstrated that the effective IFA dose was reduced by sixteen folds.
Infection efficiencies in vivo were determined using a reporter gene-bearing vector in a mammary cancer cell-derived xenograft tumor mouse model.
American Psychological Association (APA)
Klein, Reinhard& Ruttkowski, Bärbel& Schwab, Sonja& Peterbauer, Thomas& Salmons, Brian& Günzburg, Walter H.…[et al.]. 2008. Mouse Mammary Tumor Virus Promoter-Containing Retroviral Promoter Conversion Vectors for Gene-Directed Enzyme Prodrug Therapy are Functional In Vitro and In Vivo. BioMed Research International،Vol. 2008, no. 2008, pp.1-10.
https://search.emarefa.net/detail/BIM-1027037
Modern Language Association (MLA)
Klein, Reinhard…[et al.]. Mouse Mammary Tumor Virus Promoter-Containing Retroviral Promoter Conversion Vectors for Gene-Directed Enzyme Prodrug Therapy are Functional In Vitro and In Vivo. BioMed Research International No. 2008 (2008), pp.1-10.
https://search.emarefa.net/detail/BIM-1027037
American Medical Association (AMA)
Klein, Reinhard& Ruttkowski, Bärbel& Schwab, Sonja& Peterbauer, Thomas& Salmons, Brian& Günzburg, Walter H.…[et al.]. Mouse Mammary Tumor Virus Promoter-Containing Retroviral Promoter Conversion Vectors for Gene-Directed Enzyme Prodrug Therapy are Functional In Vitro and In Vivo. BioMed Research International. 2008. Vol. 2008, no. 2008, pp.1-10.
https://search.emarefa.net/detail/BIM-1027037
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1027037