Abstract 570: Long-term efficacy and downstream mechanism of anti-Annexin A2 monoclonal antibody in a pre-clinical model of aggressive human breast cancer

Abstract

Abstract Abstract: There are considerable direct evidences to support that calcium binding protein ANX A2 is a potential target for aggressive breast cancer. The most compelling evidence is based on the fact that ANX A2 overexpress specifically in aggressive triple negative human breast cancer (TNBC) cell lines as well as in human breast cancer tissues. Previously, we and others have demonstrated a unique role of ANX A2 in cancer invasion including breast cancer. Moreover we demonstrated that anti-ANX A2 monoclonal antibody (anti-ANX A2mAb)-mediated immunoneutralization of ANX A2 inhibited invasive human breast growth in a xenograft model. We further evaluated long-term effect of multiple treatments of anti-ANX A2mAb and its mechanism of inhibition of human breast tumor growth. We now show that three treatments of anti-ANX A2mAb showed significant inhibition of breast tumor growth in immunodeficient mice and anti-tumor response was started from day 94. After treatments, we followed tumor growth for 172 days and our results demonstrated 67% inhibition of tumor growth without detectable adverse effects. Biochemical analysis demonstrated anti-ANX A2mAb treatment caused significant inhibition of tissue plasminogen activator (tPA) synthesis in the tumor microenvironment. This led to disruption of plasmin generation that consequently inhibited activation of MMP-9 and MMP-2. These results suggest that ANX A2 plays an important role in aggressive breast tumor growth by regulating proteolytic pathway in the tumor microenvironment. ANX A2 may represent a new target for the development of therapeutics for the treatment of aggressive breast cancer. Citation Format: Mahesh C. Sharma, George P. Tuszynski, Marc R. Blackman, Meena Sharma. Long-term efficacy and downstream mechanism of anti-Annexin A2 monoclonal antibody in a pre-clinical model of aggressive human breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 570.