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 protein with extensive homology to the epidermal growth factor receptor. It is overexpressed in several human cancers of epithelial origin, such as 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.


METHODS
TAL from malignant ascites of a HLA-A2+ pancreatic cancer patient whose tumor overexpressed HER2/neu were stimulated 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.
Peiper
M
M
Abteilung für Allgemeinchirurgie, Universitäts-Krankenhaus Eppendorf, Universität Hamburg, Germany. PEIPER@UKE.UNI-HAMBURG.DE
Goedegebuure
P S
PS
Izbicki
J R
JR
Eberlein
T J
TJ
D000230:Adenocarcinoma / Q000276:immunology* / Q000473:pathology; D015703:Antigens, CD / Q000032:analysis; D001201:Ascites / Q000276:immunology* / Q000473:pathology; D005260:Female; D015789:HLA-A2 Antigen / Q000032:analysis; D006801:Humans; D016130:Immunophenotyping; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology
D015703:Antigens, CD; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases; C000715470:MAS1 protein, human