Intracellular antibody against erbB-2 mediates targeted tumor cell eradication by apoptosis.
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.
Deshane
J
J
Gene Therapy Program, University of Alabama, Birmingham 35294, USA.
Grim
J
J
Loechel
S
S
Siegal
G P
GP
Alvarez
R D
RD
Curiel
D T
DT
D000906:Antibodies / Q000276:immunology* / Q000627:therapeutic use; D017209:Apoptosis / Q000235:genetics*; D002452:Cell Count; D002467:Cell Nucleus / Q000737:chemistry; D003602:Cytotoxicity, Immunologic; D004249:DNA Damage / Q000187:drug effects; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D007167:Immunotherapy; D010051:Ovarian Neoplasms / Q000503:physiopathology* / Q000628:therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000906:Antibodies; D018719:Erb-b2 Receptor Tyrosine Kinases