Anti-HER2/neu Peptide Producing Vector System for Biologic Therapy - Is It Possible to Mass-produce the Peptide?.
- Author:
Byeong Woo PARK
1
;
Ki Suk KIM
;
Min Kyu HEO
;
Kyong Sik LEE
;
Eun Kyung KIM
;
Kyung Sup KIM
Author Information
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords: HER2/neu; mimetic peptide; biologic therapy
- MeSH: Amino Acid Sequence; Animals; Cell Division/drug effects; Cell Line; Mice; Oligopeptides/chemical synthesis/pharmacology; Peptide Fragments/*chemical synthesis/*pharmacology; Receptor, erbB-2/*chemistry; Recombinant Proteins/chemical synthesis/pharmacology; Support, Non-U.S. Gov't; *Technology, Pharmaceutical; Transfection
- From:Yonsei Medical Journal 2003;44(1):58-64
- CountryRepublic of Korea
- Language:English
- Abstract: 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.
