Novel gene therapy strategy to accomplish growth factor modulation induces enhanced tumor cell chemosensitivity

erbB-2 is a cell surface transmembrane glycoprotein which, when overexpressed, has been shown to be relevant to intrinsic tumor cell chemoresistance. Thus, strategies to down-regulate cell surface erbB-2 have resulted in enhanced tumor cell chemosensitivity. We have recently reported a gene therapy...

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Bibliographic Details
Published in:Clinical cancer research 1996-07, Vol.2 (7), p.1089-1095
Main Authors: BARNES, M. N, DESHANE, J. S, SIEGAL, G. P, ALVAREZ, R. D, CURIEL, D. T
Format: Article
Language:English
Subjects:
Antineoplastic agents
Biological and medical sciences
Cisplatin - pharmacology
Down-Regulation
Female
Genetic Therapy
Humans
Immunoglobulin Fragments - genetics
Immunotherapy
Medical sciences
Neoplasms - therapy
Pharmacology. Drug treatments
Receptor, ErbB-2 - antagonists & inhibitors
Receptor, ErbB-2 - immunology
Tumor Cells, Cultured
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Summary:erbB-2 is a cell surface transmembrane glycoprotein which, when overexpressed, has been shown to be relevant to intrinsic tumor cell chemoresistance. Thus, strategies to down-regulate cell surface erbB-2 have resulted in enhanced tumor cell chemosensitivity. We have recently reported a gene therapy strategy to down-modulate erbB-2 expression using a plasmid construct encoding an intracellular single chain antibody. Therefore, we now demonstrate enhanced chemosensitivity to cis-diamminedichloroplatinum in erbB-2 overexpressing tumor cells and a model system of stable clones using an intracellular single chain antibody. These findings are consistent with the hypothesis that erbB-2 plays a role in tumor cell chemoresistance. In addition, these findings represent a novel gene therapy approach to overcome erbB-2-mediated tumor cell chemoresistance.
ISSN:1078-0432
1557-3265