Abstract 4406: A monoclonal antibody targeting PAUF inhibits metastasis of pancreatic cancer

Abstract

Abstract Pancreatic cancer is one of the deadliest human tumors and, due to lack of effective therapeutic agents and diagnostic tools, has a poor prognosis with approximately a five-year survival rate of less than 5%. This disease is characterized by early metastatic spread but the process of tumor cell dissemination is largely unknown. Recently, we have shown that a novel soluble protein named PAUF (Pancreatic Adenocarcinoma Up-regulated Factor) plays an important role in the metastasis and progression of the disease. The expression of CXCR4 is induced by PAUF, implicating a role of PAUF in the organ specific metastasis of pancreatic cancer. The tumorigenic and metastatic activity of PAUF suggests that PAUF could be a target for pancreatic cancer immunotherapy. To examine the therapeutic potential of PAUF, a human monoclonal antibody against PAUF (8F3) has been generated. The 8F3 antibody exerted inhibition of migration, invasion, adhesion and proliferation of pancreatic cancer cells in vitro. In combination with gemcitabine, 8F3 showed additive effect on reduction of cell growth. In orthotopically xenografted mouse model, these anti-tumor activities of 8F3 converted to growth retardation and repression of metastasis. The level of PAUF in tumor and serum from 8F3 treated mouse was lower than that of control mouse. The immunohistochemical analysis revealed that the treatment of 8F3 inhibited the proliferation and CXCR4 expression in both primary and metastasized tumors. The 8F3 antibody also alters intracellular signaling which was induced by PAUF. We will also discuss about the effect of 8F3 in tumor microenvironment, especially recruitment of immune cells. Collectively, these findings indicate that PAUF has a therapeutic potential for treatment of human pancreatic cancer and the 8F3 antibody can be developed for therapeutic agent for this disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4406.