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  • Title: Intracellular antibody against erbB-2 mediates targeted tumor cell eradication by apoptosis.
    Author: Deshane J, Grim J, Loechel S, Siegal GP, Alvarez RD, Curiel DT.
    Journal: Cancer Gene Ther; 1996; 3(2):89-98. PubMed ID: 8729907.
    Abstract:
    Methods were developed to achieve targeted eradication of the erbB-2 oncoprotein using gene constructs encoding anti-erbB-2 intracellular single-chain antibodies. This method of genetic intervention caused a marked cytocidal effect in erbB-2-overexpressing human ovarian tumor cells. Evaluation of the mechanistic basis of this phenomenon demonstrated that programmed cell death had been induced. Significantly, no cytocidal effect was observed in non-erbB-2-overexpressing tumors. The induction of apoptosis could be shown to be secondary to the intracellular antibody-mediated ectopic localization of the erbB-2 oncoprotein. Thus, the strategy of selective oncogene "knock-out" using intracellular antibodies represents a novel anticancer gene therapy strategy that offers the potential to achieve highly specific, targeted eradication of human tumor cells.
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