Cancer is an important public health issue in US and worldwide. Every year, more than 1.2 million Americans are diagnosed with invasive carcinomas; half of them will eventually die from the diease or disease-related complications. These statistics make cancer the second leading cause of death in adults in US. Traditional treatments such chemotherapy and ionizing radiation have proven ineffective in treating the majority of human malignancies, usually due to toxicity or development of resistance. Recently, special attention has been given to drugs that inhibit tumor growth and metastasis by suppressing the formation of tumor vasculature. Tumor angiogenesis, defined as the formation of tumor blood capillaries from pre-existing vessels via proliferation and migration of endothelial cells, is considered to be a distinct and required step in cancer development. Ergon Pharmaceuticals wishes to develop monoclonal antibodies that inhibit tumor angiogenesis by targeting an intracellular protein, which is expressed on the cell surface of endothelial cells under pathological conditions such as hypoxia and acidosis. This protein represents a novel and unexplored target for development of novel anticancer proteins. Funding from this SBIR Phase grant will support production of antibodies and characterization of their biological properties in a variety of in vitro angiogenesis assays, including endothelial cell proliferation and migration. Successful completion of Phase 1 studies will allow Ergon Pharmaceuticals to apply for Phase II funding in order: a. to investigate the ability of these antibodies to inhibit tumor growth in a variety of syngeneic and allogeneic primary and metastatic murine tumor models, b. to select the best performing antibody for humanization, and c. to test the humanized antibody in acute and chronic toxicology studies in preparation for the submission of an IND with the FDA
