title: Gene therapy using plasmid DNA-encoded anti-HER2 antibody for cancers that overexpress HER2.
abstract: Plasmid DNA-encoded antibodies, or DNA-based monoclonal antibodies (dMAbs), are delivered by intramuscular injection and in vivo electroporation (EP) and are effective in virus neutralization, although they have not been evaluated for tumor gene therapy. Here we investigated whether a dMAb was appropriate for tumor gene therapy. We constructed the expression plasmids coding for the heavy or light chain of a parental murine antibody of Herceptin with the antibody genes codon- and RNA-optimized and fused to the Kozak-IgE leader sequence in pVax1. Transfection of the plasmids into human muscle RD cells resulted in functional expression of the antibody, and this exhibited the same in vitro antiproliferative activity as Herceptin. A single intramuscular injection and in vivo EP of the plasmids (100 μg per head) resulted in high and sustained antibody expression in the sera of normal mice and in effective inhibition of tumor growth in nude mice bearing HER2-positive human breast carcinoma BT474 xenografts. The antitumor efficacy of the anti-HER2 dMAb was similar to that of four doses of intravenously injected 10 mg kg-1Herceptin. The results demonstrate that the dMAb is effective in the treatment of HER2-positive breast cancer, suggesting that this dMAb may be applicable for tumor gene therapy.
authors.affiliation: Department of Biology, College of National Science, Kangwon National University, Chuncheon, Korea.
authors.forename: H
authors.initials: H
authors.lastname: Kim
authors.affiliation: BK21 Plus Graduate Program and Department of Microbiology, School of Medicine, Kangwon National University, Chuncheon, Korea.
authors.forename: S N
authors.initials: SN
authors.lastname: Danishmalik
authors.affiliation: Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon, Korea.
authors.forename: H
authors.initials: H
authors.lastname: Hwang
authors.affiliation: BK21 Plus Graduate Program and Department of Microbiology, School of Medicine, Kangwon National University, Chuncheon, Korea.
authors.forename: J-I
authors.initials: JI
authors.lastname: Sin
authors.affiliation: Research Center, GeneOne Life Science, Seoul, Korea.
authors.forename: J
authors.initials: J
authors.lastname: Oh
authors.affiliation: Research Center, GeneOne Life Science, Seoul, Korea.
authors.forename: Y
authors.initials: Y
authors.lastname: Cho
authors.affiliation: Research Center, GeneOne Life Science, Seoul, Korea.
authors.forename: H
authors.initials: H
authors.lastname: Lee
authors.affiliation: Research Center, GeneOne Life Science, Seoul, Korea.
authors.forename: M
authors.initials: M
authors.lastname: Jeong
authors.affiliation: Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon, Korea.|University-Industry Cooperation Foundation, Kangwon National University, Chuncheon, Korea.
authors.forename: S-H
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon, Korea.|Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon, Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Hong
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D001943:Breast Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000628:therapy*; D049109:Cell Proliferation; D004247:DNA / Q000737:chemistry; D018274:Electroporation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D057809:HEK293 Cells; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology* / Q000378:metabolism*; D000068878:Trastuzumab / Q000737:chemistry
chemical_list: D000911:Antibodies, Monoclonal; D004247:DNA; D007074:Immunoglobulin G; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human