Cancer Therapy: Preclinical BCMab1, A Monoclonal Antibody against Aberrantly Glycosylated Integrin a3b1, Has Potent Antitumor Activity of Bladder Cancer In Vivo

Purpose: To identify a novel biomarker for bladder cancer targeting therapy. ExperimentalDesign: Thehumanbladder cancer cell line T24 cellswere used as immunogen to generate mouse monoclonal antibodies. We screened and identified a specific antibody BCMab1 against bladder cancer. We examined BCMab1 antigen expression in the patients with bladder cancer through immunohistochemical staining and investigated the BCMab1 antigen association with clinical severity. We detected the antitumor activity of BCMab1 antibody and investigated its therapeutic efficacy by subcutaneous and orthotopic bladder cancer models. Results: We developed a new monoclonal antibody BCMab1 against bladder cancer that specifically recognized the aberrantly glycosylated Integrin a3b1 epitope on bladder cancer cells. Expression of the BCMab1 antigen was consistent with clinical severity and prognosis of bladder cancer. The glycosyltransferase GALNT1 could contribute to aberrant glycosylation of Integrin a3. The aberrant glycosylation of integrin a3–activated integrin signaling to initiate FAK activation. BCMab1 could block Integrin engagement to inhibit its signaling leading to cell-cycle arrest. In addition, BCMab1 enhanced FcgR-dependent antitumor activity in vivo. Conclusions: BCMab1 antigen is a new biomarker for bladder cancer. BCMab1 antibody exhibited potent antitumor activity against bladder cancer in vivo. Clin Cancer Res; 20(15); 4001–13. 2014 AACR.