Anti-synthetic peptide antibody reacting at the fusion junction of deletion-mutant epidermal growth factor receptors in human glioblastoma

Peter A. Humphrey, Albert J. Wong, Bert Vogelstein, Michael R. Zalutsky, Gregory N. Fuller, Gerald E. Archer, Henry S. Friedman, Madan M. Kwatra, Sandra H. Bigner, Darell D. Bigner

Research output: Contribution to journalArticlepeer-review

Abstract

We have investigated human gliomas that plify and rearrange the epidermal growth factor receptor gane, with generation of an in-frame deletion mutation of 802 gacleotides in the external domain. This in-frame deletion mutation generates a local amino acid sequence at the fusion junction of what normally were distant polypeptide sequences acid the intact epidermal growth factor receptor. This 14-amino peptide was chemically synthesized, coupled to keyhole elicited antibody hemocyanin, and used as an immunogen in rabbits. The elicited antibody reacted specifically with the fusion peptide in ELISA. The anti-fusion junction peptide antibody was purified by passage of the antiserum over a peptide affinity column with scidic elution. The purified antibody selectively bound the glioma deletion mutant as compared to the intact epidermal growth factor receptor as assessed by immunocytochemistry, immunofluorescence, immunoprecipitation with gel electrophoresis, and binding experiments using radioiodinated antibody. These data indicate that it is feasible to generate site-specific anti-peptide antibodies that are highly selective for mutant proteins in human tumors. The anti-peptide antibody described here, and other mutation site-specific antibodies, should be ideal candidates for tumor immunoimaging and immunotherapy. (.

Original languageEnglish (US)
Pages (from-to)4207-4211
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number11
DOIs
StatePublished - 1990

Keywords

  • Brain tumor
  • Peptide immunization
  • Protooncogene
  • c-erbB

ASJC Scopus subject areas

  • General

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