Connective Tissue Growth Factor (CTGF) is a central mediator of tissue remodeling. It acts downstream from both VEGF and TGFbeta to recruit and activate tissue-remodeling cells, including fibroblasts and endothelial cells. In the tumor, CTGF mediates stromal response to tumor growth, including angiogenesis. We propose to apply the FibroGen library of human monoclonal antibodies to the suppression of CTGF function in tumor growth and development. After establishment of a CTGF-driven angiogenic model in mice using recombinant collagen and CTGF, the library will be screening for anti-angiogenic activity. The most effective antibodies will be further developed in Phase II of this project as anticancer agents. These antibodies will be capable of restricting stromal angiogenic responses to tumors, thereby starving the tumor for oxygen and nutrients. CTGF has been found in high concentrations in a wide range of tumors and leukemias. The anti-angiogenic antibodies developed in this project will find application in both primary and late stage therapeutic responses to cancer.
Thesaurus Terms: angiogenesis inhibitor, antineoplastic, connective tissue growth factor, drug design /synthesis /production, immunologic substance development /preparation, monoclonal antibody collagen, neoplasm /cancer remission /regression, recombinant protein laboratory mouse
