Gene therapy using plasmid DNA-encoded anti-HER2 antibody for cancers that overexpress HER2.

Autor: Kim H; Department of Biology, College of National Science, Kangwon National University, Chuncheon, Korea., Danishmalik SN; BK21 Plus Graduate Program and Department of Microbiology, School of Medicine, Kangwon National University, Chuncheon, Korea., Hwang H; Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon, Korea., Sin JI; BK21 Plus Graduate Program and Department of Microbiology, School of Medicine, Kangwon National University, Chuncheon, Korea., Oh J; Research Center, GeneOne Life Science, Seoul, Korea., Cho Y; Research Center, GeneOne Life Science, Seoul, Korea., Lee H; Research Center, GeneOne Life Science, Seoul, Korea., Jeong M; Research Center, GeneOne Life Science, Seoul, Korea., Kim SH; Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon, Korea.; University-Industry Cooperation Foundation, Kangwon National University, Chuncheon, Korea., Hong HJ; Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon, Korea.; Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon, Korea.
Jazyk: angličtina
Zdroj: Cancer gene therapy [Cancer Gene Ther] 2016 Oct; Vol. 23 (10), pp. 341-347. Date of Electronic Publication: 2016 Sep 16.
DOI: 10.1038/cgt.2016.37
Abstrakt: 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 -1 Herceptin. 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.
Databáze: MEDLINE
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