Annexin a2 as immunological target

Abstract

AnnexinA2 (ANXA2), a member of the Annexin family of calcium-dependent, phospholipid binding proteins, is one of a panel of identified antigens recognized by the post-vaccination sera of patients who demonstrated prolonged disease-free survival following multiple vaccinations. AnnexinA2 is abundantly expressed in pancreatic adenocarcinomas and cell surface / membrane AnnexinA2 increases with the progression from premalignant lesions to invasive pancreatic adenocarcinomas. The cytoplasmic to cell surface translocation of AnnexinA2 expression is critical for pancreatic cancer cell invasion. In addition, phosphorylation of AnnexinA2 at Tyrosine 23 is important for its localization to the cell surface and for the invasion of pancreatic cancer cells. Finally, loss of AnnexinA2 leads to the loss of the Epithelial-Mesenchymal Transition.

Description

[0001] This invention was made in part using funds from the National Institutes of Health, Grant No. P50CA062924. The U.S. Government retains certain rights in the invention according to the terms of the grant.TECHNICAL FIELD OF THE INVENTION

[0002] This invention is related to the area of tumor immunology. In particular, it relates to highly immunogenic proteins found on tumor cells.BACKGROUND OF THE INVENTION

[0003] Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignant disease with a median survival of less than 6 months and an overall 5-year survival rate of 1-4% (Pierantoni, Pagliacci et al. 2008). Lack of early diagnosis and effective systemic treatment are major reasons that account for these dismal survival rates. Morphologic and genetic analyses have implicated pancreatic intraepithelial neoplasm (PanIN) as a precursor lesion of human PDAC. PanINs appear to evolve in a stepwise manner through stages (PanIN1A, 1B, 2, 3) that display increasing cellular atypia and accu...

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