Abstract 3666: Inhibition of the tumor growth and prevention of metastases with MORAb-004, a human monoclonal IgG targeting endosialin/TEM-1

Abstract

Abstract Endosialin/Tumor Endothelial Marker-1 (TEM-1) is a cell surface glycoprotein that is expressed on cells involved in the development of tumor vasculature, primarily pericytes, smooth muscle, and stromal fibroblasts. Studies have found endosialin to play a key role in tumor growth and neovessel formation in numerous cancer types including (but not limited to) renal, breast, colon, pancreatic, lung, endometrial, ovarian, melanoma, sarcoma, and neuroectodermal tumors. We are currently evaluating the therapeutic efficacy of MORAb-004, a human monoclonal IgG1 targeting TEM-1, in a Phase I clinical trial. Because MORAb-004 only recognizes human/monkey TEM-1 and has no cross-reactivity with rodent TEM-1, we generated a human TEM-1 knock-in mouse line in order to assess its activity in in vivo tumor models. In a B16-F10 subcutaneous melanoma model we found that MORAb-004 significantly inhibited tumor progression by ∼70%. Moreover, using the Lewis Lung Carcinoma model of metastatic disease our results showed that MORAb-004 had a significant inhibitory effect on the number of lung metastases. Taken together our results demonstrated the ability of MORAb-004 in inhibiting the growth of solid tumors and preventing the emergence of distant metastases. The potential MOA is currently under evaluation and will be discussed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3666. doi:10.1158/1538-7445.AM2011-3666