Specific inhibition of the reaction between a tumor-inhibitory antibody and the ErbB-2 receptor by a mimotope derived from a phage display library

Nora Vaisman, Ahuva Nissim, Leah N. Klapper, Boaz Tirosh, Yosef Yarden, Michael Sela*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Overexpression of ErbB-2, a coreceptor for stroma-derived growth factors, is involved in malignancies of epithelial tissues, and a humanized antibody to ErbB-2 was shown to be therapeutic in a clinical setting. In an effort to understand and enhance immunotherapy, the laboratory has raised several tumor inhibitory monoclonal antibodies (mAb), including mAb L26 that blocks inter-receptor interactions. Here the application of the phage display methodology for the isolation of a phage clone that specifically recognizes mAb L26 is described. The isolated mimetic peptide (mimotope) specifically inhibited the binding of mAb L26 to ErbB-2 overexpressing cells. No sequence homology was found between the mimotope and ErbB-2, implying that it mimics a conformational structure of the receptor. Preliminary studies showed that the lead peptide can be truncated by removal of two to three amino acids from either the N- or C-terminal end without drastically affecting the inhibitory properties of the mimotope. A tryptophan/glycine residue at the C-terminus and a lysine at the N-terminus of the peptide seemed to play a role in its ability to compete with L26 antibody for binding to ErbB-2 overexpressing cells. These results highlight the potential of active immunization with conformation mimicking peptides in ErbB-2 overexpressing tumors.

Original languageAmerican English
Pages (from-to)61-67
Number of pages7
JournalImmunology Letters
Volume75
Issue number1
DOIs
StatePublished - 1 Dec 2000
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the Bristol-Meyers Squibb Foundation Center Grant award to M.S. We thank Dr G. Winter from M.R.C., Cambridge, UK, for providing the phage library. We thank Professor M. Fridkin for help with peptide synthesis.

Keywords

  • Antibodies
  • ErbB-2
  • Mimotope
  • Phage display

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