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

Background: The proto-oncogene HER2/neu encodes a 185 kDa transmembrane pro tein with extensive homology to the epidermal growth factor receptor. It is overexpressed in several human cancers of epithelial origin, such as pancr eatic cancer. Previously we demonstrated that CTL derived from breast, ovar ian, and non-small cell lung cancer recognized a peptide derived fi om HER2 /neu. The aim of this study was to evaluate whether this HLA-A2-binding pep tide is a TAA in pancreatic cancer and if pancreatic cancer associated T-ly mphocytes (TAL) are useful to generate tumor- and peptide-specific CTL. Mat erials and Methods: TAL fi om malignant ascites of a HLA-A2(+) pancreatic c ancer patient whose tumor overexpressed HER2/neu were stimulated on solid-p hase anti-CD3 and cultured in low-dose IL-2. Using repetitive autologous tu mor cell stimulation, CTL were generated Results: CTL recognized autologous and allogeneic HER2/neu (+) tumor cells in an HLA-A2 restricted fashion si gnificantly. Furthermore, all CTL recognized p654-662 (GP2) derived from HE R2/neu, but not the control peptide. Conclusions: These results demonstrate that this HER2/neu derived peptide is a TAA ii? pancreatic carcinoma. The identification of the HER2/neu derived peptide GP2 as a TAA in pancreatic c ancer provides an opportunity for the design of novel immunotherapy and vac cine strategies. The possibility of generating peptide-specific CTL from ma lignant ascites enables future studies to identify more antigens in this di sease.