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Rationally designed anti-HER2/neu peptide mimetic disables P185HER2/neu tyrosine kinases in vitro and in vivo

Authors
 Byeong-Woo Park  ;  Hong-Tao Zhang  ;  Chuanjin Wu  ;  Alan Berezov  ;  Xin Zhang  ;  Raj Dua  ;  Qiang Wang  ;  Gary Kao  ;  Donald M. O'Rourke  ;  Mark I. Greene  ;  Ramachandran Murali 
Citation
 Nature Biotechnology, Vol.18(2) : 194-198, 2000 
Journal Title
NATURE BIOTECHNOLOGY
ISSN
 1087-0156 
Issue Date
2000
MeSH
Animals ; Antibodies, Monoclonal/chemistry* ; Antibodies, Monoclonal/pharmacology* ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/chemistry* ; Apoptosis ; Astrocytoma ; Biosensing Techniques ; Doxorubicin/therapeutic use ; Drug Design ; Drug Therapy, Combination ; Gamma Rays ; Mice ; Mice, Nude ; Molecular Mimicry* ; Protein Binding ; Radiotherapy, Adjuvant ; Receptor, ErbB-2/antagonists & inhibitors* ; Trastuzumab ; Tumor Cells, Cultured/drug effects ; Tumor Cells, Cultured/radiation effects
Abstract
Monoclonal antibodies specific for the p185HER2/neu growth factor receptor represent a significant advance in receptor-based therapy for p185HER2/neu-expressing human cancers. We have used a structure-based approach to develop a small (1.5 kDa) exocyclic anti-HER2/neu peptide mimic (AHNP) functionally similar to an anti-p185HER2/neu monoclonal antibody, 4D5 (Herceptin). The AHNP mimetic specifically binds to p185HER2/neu with high affinity (KD=300 nM). This results in inhibition of proliferation of p185HER2/neu-overexpressing tumor cells, and inhibition of colony formation in vitro and growth of p185HER2/neu-expressing tumors in athymic mice. In addition, the mimetic sensitizes the tumor cells to apoptosis when used in conjunction with ionizing radiation or chemotherapeutic agents. A comparison of the molar quantities of the Herceptin antibody and the AHNP mimetic required for inhibiting cell growth and anchorage-independent growth showed generally similar activities. The structure-based derivation of the AHNP represents a novel strategy for the design of receptor-specific tumor therapies.
Full Text
http://www.nature.com/articles/nbt0200_194
DOI
10.1038/72651
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Park, Byeong Woo(박병우) ORCID logo https://orcid.org/0000-0003-1353-2607
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/171810
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