Investigating a novel recombinant antibody to attenuate prostate cancer progression by targeting cell surface GRP78.

206Background: Prostate cancer (PCa) is characterized by increased activation of the procoagulant protein, tissue factor (TF) that drive tumour progression. We now show that this process is modulated by GRP78 on the cell surface (cs). In PCa GRP78 is a endoplasmic reticulum-resident chaperone that localizes to the cell surface where it functions as a signaling molecule with antigenic properties. In response to csGRP78 presentation, PCa patients produce autoantibodies (AutoAbs) against the N-terminus of GRP78. AutoAbs:csGRP78 complex acts as a potent driver of tumor growth via upregulation of the unfolded protein response (UPR) and TF activity. We hypothesize that inhibiting the binding of anti-GRP78 AutoAbs to csGRP78 will supress UPR and TF activity. Here we describe a recombinant anti-GRP78 antibody (AEP8587) that competes with the binding of AutoAbs to csGRP78 and may act as a novel therapeutic antibody with antitumor activity. Methods: Changes in TF activity or UPR markers were evaluated in vitro in t...