Type I Collagen as an Anti-Tumor Target

DESCRIPTION: (provided by applicant) Many diseases require the development of blood vessels for the pathological state, including cancer, vascular eye diseases, and arthritis. A novel target (namely Type I collagen) for inhibiting the development of new blood vessels has been suggested by the work of one of CMls founders. The application aims to identify antagonists (in the form of monoclonal antibodies) that specifically recognize cryptic sites in Type I collagen that are exposed during the process of vessel formation. Among these Mabs will be antagonists that target cryptic regulatory sites that are required for the completion of angiogenesis. These Mabs, and other antagonists that bind to the same site could potentially be potent angiogenesis inhibitors, and will have application in treating cancers and other diseases. Because these cryptic sites in Type I collagen are exposed predominately in angiogenic tissues, these Mabs will be useful in the diagnosis of cancer and other diseases. Three specific aims are proposed: Aim 1: Identify a set of monoclonal antibodies (Mabs) that react with denatured, but not native, Type I collagen. Aim 2: Test the effects of the Mabs that react with denatured Type I collagen on endothelial and tumor cell behavior in vitro. Aim 3: Test the Mabs isolated in Aim 1 in chick chorioallantoic membrane (CAM) angiogenesis assays for anti-angiogenic activities. PROPOSED COMMERCIAL APPLICATION: Antagonists of cryptic sites in type I collagen that block angiogenesis and tumor growth have commercial applications as treatment and diagnosis for cancers and other diseases with abnormal vessel development. These disease affects millions of patients each year. Pharmaceutical sales for the treatment and diagnosis of these diseases is in excess of 2 billion dollars annually. The products developed under this proposal could capture a significant percent of these sales.