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 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.
Barnes
M N
MN
Departments of Obstetrics and Gynecology and Pathology, Cell Biology, and Surgery, and Gene Therapy Program, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Deshane
J S
JS
Siegal
G P
GP
Alvarez
R D
RD
Curiel
D T
DT
D002945:Cisplatin / Q000494:pharmacology*; D015536:Down-Regulation; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D007128:Immunoglobulin Fragments / Q000235:genetics*; D009369:Neoplasms / Q000628:therapy*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000276:immunology*; D014407:Tumor Cells, Cultured
D002945:Cisplatin; D007128:Immunoglobulin Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; C055966:immunoglobulin Fv