Pancreatic cancer associated ascites-derived CTL recognize a nine-amino-acid peptide GP2 derived from HER2/neu

Matthias Peiper, Peter S. Goedegebuure, Jakob R. Izbicki, Timothy J. Eberlein

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10 Scopus citations

Abstract

Background: The proto-oncogene HER2/neu encodes a 185 kDa transmembrane protein with extensive homology to the epidermal growth factor receptor. It is overexpressed in several human cancers of epithelial origin, such a pancreatic cancer. Previously, we demonstrated that CTL derived from breast, ovarian, and non-small cell lung cancer recognized a peptide derived from HER2/neu. The aim of this study was to evaluate whether this HLA-A2-binding peptide is a TAA in pancreatic cancer and if pancreatic cancer associated T-lymphocytes (TAL) are useful to generate tumor- and peptide-specific CTL. Material and Methods: TAL from malignant ascites of a HLA-A2+ pancreatic cancer patient whose tumor overexpressed HER2/neu were stimulates on solid-phase anti-CD3 and cultured in low-dose IL-2. Using repetitive autologous tumor cell stimulation, CTL were generated. Results: CTL recognized autologous and allogeneic HER2/neu+ tumor cells in an HLA-A2 restricted fashion significantly. Furthermore, all CTL recognized p654-662 (GP2) derived from HER2/neu, but not the control peptide. Conclusions: These results demonstrate that this HER2/neu derived peptide is a TAA in pancreatic carcinoma. The identification of the HER2/neu derived peptide GP2 as a TAA in pancreatic cancer provides an opportunity for the design of novel immunotherapy and vaccine strategies. The possibility of generating peptide-specific CTL from malignant ascites enables future studies to identify more antigens in this disease.

Original languageEnglish
Pages (from-to)2471-2475
Number of pages5
JournalAnticancer research
Volume19
Issue number4 A
StatePublished - Jan 1 1999

Keywords

  • CTL-HER2/neu
  • Pancreatic cancer
  • Tumor-associated antigen

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