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- W2896754866 abstract "3006 Angiopoietin Related Proteins (ARPs) play a pivotal role in vascular formation and homeostasis. ARP4, a secreted protein, retains the characteristic angiopoietin family N-terminal coiled-coil domain and C-terminal fibrinogen-like domain. RTQ PCR analysis revealed transcript expression predominantly in adipose and liver tissues. Strikingly, ARP4 mRNA expression is also elevated in clear cell renal carcinoma as compared to adjacent non-tumor tissue suggesting a role in the neovascularization and progression of this disease. Our results confirm and extend the proposed role of ARP4 in the angiogenesis and progression of renal carcinoma. In this study, we report the biological characterization of purified recombinant ARP4 and that it acts both as a proangiogenic factor for endothelial cells and as a survival factor for 786-0 renal carcinoma cells. Based on these observations, we hypothesized that a monoclonal antibody raised against ARP4 might inhibit ARP4-induced activities and be useful in the treatment of renal carcinoma. Therefore, fully human ARP4 monoclonal antibodies (CR064) were generated using XenoMax technology. Selection criteria for CR064 mAbs included potent affinity, binding specificity and the ability to inhibit ARP4-mediated HUVEC migration as well as 786-0 cell survival. At a concentration of 250ng/ml, ARP4 caused approximately 2-fold enhancement of HUVEC migration and induced tube formation in matrigel. The effects of ARP4 on HUVEC migration were inhibited by CR064 in a dose dependent manner with an IC50 of 7nM. The enhancement of tube formation was also blocked at an IC50 of 27 nM. Coincidently, ARP4 (500ng/ml) caused an increase in the survival of 786-0 cells which was inhibited by CR064 monoclonal antibodies in a dose dependent manner (IC50 of 27nM). Taken together, these data suggest that CR064, a fully human monoclonal antibody against ARP4, plays a dual role in that it inhibits both ARP4-mediated angiogenesis and survival of renal carcinoma cells in vitro . These observations support further investigation of CR064 fully human monoclonal antibodies that neutralize ARP4 activities for the treatment of renal cell carcinoma." @default.
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- W2896754866 date "2005-05-01" @default.
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- W2896754866 title "CR064, a fully human monoclonal antibody to angiopoietin related protein 4 (ARP4) inhibits ARP4-mediated angiogenesis and renal cell carcinoma survival in vitro" @default.
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