Anti-HER2/neu peptide producing vector system for biologic therapy - is it possible to mass-produce the peptide?
A humanized monoclonal antibody against HER2 has been using in a clinical setting and has been shown to possess therapeutic properties. A mimetic peptide against HER2 was also reported to bind to the HER2 receptor with some therapeutic potential. Based on a previous report and the sequence of Herceptin, we designed oligonucleotides of anti-HER2 mimetic peptides, named V2 and V3 peptides, in order to develop a peptide- producing vector system for biologic therapy against HER2- overexpressing cancers. We also adopted the sequence of a previously reported mimetic peptide, V1 (Park BW et al. Nat. Biotechnol, 2000, 18:194-198), as a reference peptide. We examined the effects of the V2 and V3 peptides against the HER2-overexpressing cell lines, SK-BR-3 and T6-17. Transient transfection of the construct expressing V1 and V2 inhibited cell proliferation in HER2-overexpressing cell lines by 20 - 30%, but had no effect on the HER2-negative NIH3T3 cells. The proliferation inhibition shown by V2 was slightly better than that shown by V1. Recombinant peptides V2 and V3 were produced on a large scale in an E. coli system, and the V2 peptide showed anti-HER2-specific tumor cell proliferation inhibition of 10% to 30%. Current results suggest that anti-HER2 mimetic peptides, overexpressed by a constitutive promoter or produced in an E. coli system, could specifically inhibit the proliferation of HER2-expressing cancer cells. Further efforts to augment the biologic specificity and efficacy and to develop new technologies for the purification of the peptide from the E coli system are needed.
Park
Byeong Woo
BW
Department of Surgery, Yonsei University College of Medicine, 134 Shinchon- dong, Seodaemun-gu, Seoul 120-752, Korea. bwpark@yumc.yonsei.ac.kr
Kim
Ki Suk
KS
Heo
Min Kyu
MK
Lee
Kyong Sik
KS
Kim
Eun Kyung
EK
Kim
Kyung Sup
KS
D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D051379:Mice; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry*; D011994:Recombinant Proteins / Q000138:chemical synthesis / Q000494:pharmacology; D013678:Technology, Pharmaceutical; D014162:Transfection
D009842:Oligopeptides; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; D011994:Recombinant Proteins