Abstract
Monoclonal antibodies specific for the p185(HER2/neu) growth factor receptor represent a significant advance in receptor-based therapy for p185(HER2/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-p185(HER2/neu) monoclonal antibody, 4D5 (Herceptin). The AHNP mimetic specifically binds to p185(HER2/neu) with high affinity (K(D) = 300 nM). This results in inhibition of proliferation of p185(HER2/neu)-overexpressing tumor cells, and inhibition of colony formation in vitro and growth of p185(HER2/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.
| Original language | English |
|---|---|
| Pages (from-to) | 194-198 |
| Number of pages | 5 |
| Journal | Nature Biotechnology |
| Volume | 18 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2000 Feb 1 |
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All Science Journal Classification (ASJC) codes
- Biotechnology
- Bioengineering
- Applied Microbiology and Biotechnology
- Molecular Medicine
- Biomedical Engineering
Cite this
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Rationally designed anti-HER2/neu peptide mimetic disables p185(HER2/neu) tyrosine kinases in vitro and in vivo. / Park, Byeongwoo; Zhang, Hong Tao; Wu, Chuanjin; Berezov, Alan; Zhang, Xin; Dua, Raj; Wang, Qiang; Kao, Gary; O'Rourke, Donald M.; Greene, Mark I.; Murali, Ramachandran.
In: Nature Biotechnology, Vol. 18, No. 2, 01.02.2000, p. 194-198.Research output: Contribution to journal › Article
TY - JOUR
T1 - Rationally designed anti-HER2/neu peptide mimetic disables p185(HER2/neu) tyrosine kinases in vitro and in vivo
AU - Park, Byeongwoo
AU - Zhang, Hong Tao
AU - Wu, Chuanjin
AU - Berezov, Alan
AU - Zhang, Xin
AU - Dua, Raj
AU - Wang, Qiang
AU - Kao, Gary
AU - O'Rourke, Donald M.
AU - Greene, Mark I.
AU - Murali, Ramachandran
PY - 2000/2/1
Y1 - 2000/2/1
N2 - Monoclonal antibodies specific for the p185(HER2/neu) growth factor receptor represent a significant advance in receptor-based therapy for p185(HER2/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-p185(HER2/neu) monoclonal antibody, 4D5 (Herceptin). The AHNP mimetic specifically binds to p185(HER2/neu) with high affinity (K(D) = 300 nM). This results in inhibition of proliferation of p185(HER2/neu)-overexpressing tumor cells, and inhibition of colony formation in vitro and growth of p185(HER2/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.
AB - Monoclonal antibodies specific for the p185(HER2/neu) growth factor receptor represent a significant advance in receptor-based therapy for p185(HER2/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-p185(HER2/neu) monoclonal antibody, 4D5 (Herceptin). The AHNP mimetic specifically binds to p185(HER2/neu) with high affinity (K(D) = 300 nM). This results in inhibition of proliferation of p185(HER2/neu)-overexpressing tumor cells, and inhibition of colony formation in vitro and growth of p185(HER2/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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0033953634&partnerID=8YFLogxK
U2 - 10.1038/72651
DO - 10.1038/72651
M3 - Article
C2 - 10657127
AN - SCOPUS:0033953634
VL - 18
SP - 194
EP - 198
JO - Nature Biotechnology
JF - Nature Biotechnology
SN - 1087-0156
IS - 2
ER -