NOVEL GENE-THERAPY STRATEGY TO ACCOMPLISH GROWTH-FACTOR MODULATION INDUCES ENHANCED TUMOR-CELL CHEMOSENSITIVITY

erbB-2 is a cell surface transmembrane glycoprotein which, when overex pressed, has been shown to be relevant to intrinsic tumor cell chemore sistance, Thus, strategies to downregulate cell surface erbB-2 have re sulted in enhanced tumor cell chemosensitivity. We have recently repor ted a gene therapy strategy to down-modulate erbB-2 expression using a plasmid construct encoding an intracellular single chain antibody, Th erefore, we now demonstrate enhanced chemosensitivity to cis-diammined ichloroplatinum in erbB-2 overexpressing tumor cells and a model syste m 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 ch emoresistance.