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 |
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Pages (from-to) | 194-198 |
Number of pages | 5 |
Journal | Nature Biotechnology |
Volume | 18 |
Issue number | 2 |
DOIs | |
Publication status | Published - 2000 Feb |
Bibliographical note
Funding Information:This work was supported by grants awarded to M.I.G. from the Abramson Cancer Institute, National Cancer Institute, NIH, and the US Army.
All Science Journal Classification (ASJC) codes
- Biotechnology
- Bioengineering
- Applied Microbiology and Biotechnology
- Molecular Medicine
- Biomedical Engineering