Polyclonal antibodies against gp185HER2 peptides: Their putative role in the identification of a particular HER2 status in patients with breast cancer

Francesca Di Modugno, Simonetta Buglioni, Marcella Mottolese, Duilia Del Bello, Simona Cascioli, Alberto Chersi, Angela Santoni, Paola Nisticò

Research output: Contribution to journalArticlepeer-review

Abstract

The HER2 oncogene and its relative oncoprotein, gp185HER2, a transmembrane glycoprotein belonging to the epidermal growth factor receptor family, are overexpressed in a wide range of solid tumors including breast and ovarian cancer. In patients with breast cancer, both humoral and cell-mediated HER2 immune responses have been found as well as in some patients with gp185HER2 nonoverexpressing tumors. To establish whether peptide sequences identified as HLA-A2-restricted T-cell epitopes are expressed in breast tumor cell lines and tissues, we produced and characterized by different methodologic approaches polyclonal antibodies raised against four gp185HER2 peptides. Two of the antibodies recognized peptides eluted from the HLA-A2 groove of the mDAmB231 breast cancer cell line expressing a basal level of gp 185HER2. Paraffin-embedded primary and metastatic breast tumors were specifically immunostained by all four reagents, thereby showing an overlapping reactivity. When this immunoreactivity was compared with that obtained using two different monoclonal antibodies, in 105 breast primary tumors and 36 corresponding lymph node metastases, we identified a subset of tumors that were negative with anti-gp185HER2 monoclonal antibodies and positive with the four antipeptide antibodies. Our novel observations provide in vivo evidence of the complexity involved in evaluating HER2 expression, and open a new path for understanding the biologic significance of HER2 status in breast tumors.

Original languageEnglish
Pages (from-to)221-231
Number of pages11
JournalJournal of Immunotherapy
Volume24
Issue number3
DOIs
Publication statusPublished - 2001

Keywords

  • Antipeptide antibodies
  • Breast cancer
  • HER2 status
  • HLA-A2

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

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