Type I Collagen as an Anti-Tumor Target

描述：（申请人提供） 许多疾病需要血管的发展为病理 这些疾病包括癌症、血管性眼病和关节炎。新靶点 （即I型胶原蛋白）用于抑制新血管的发育 这是由CMLS创始人之一的工作提出的。应用目的 为了鉴定拮抗剂（以单克隆抗体的形式）， 特异性识别I型胶原中暴露的隐蔽位点 在血管形成的过程中。在这些单克隆抗体中， 其目标是完成以下过程所需的神秘调控位点： 血管生成这些单克隆抗体和其他结合到同一位点的拮抗剂 可能是有效的血管生成抑制剂， 治疗癌症和其他疾病。因为I型病毒中的这些神秘位点 胶原蛋白主要暴露在血管生成组织中，这些Mab将 可用于癌症和其它疾病的诊断。三个具体目标是 目的1：鉴定一组单克隆抗体（Mab）， 用变性的但不是天然的I型胶原蛋白。目标2：测试 与变性I型胶原反应的内皮和肿瘤单克隆抗体 体外细胞行为目的3：在鸡中检测目的1中分离的单克隆抗体 用于抗血管生成的绒毛膜尿囊膜（CAM）血管生成测定 活动 拟定商业应用： 阻断血管生成和肿瘤生长的I型胶原隐蔽位点拮抗剂 具有作为癌症和其它疾病的治疗和诊断的商业应用 血管发育异常 这些疾病每年影响数百万患者。 用于治疗和诊断这些疾病的药品销售额超过 20亿美元。 根据这一建议开发的产品可以获得 这些销售额的很大一部分。

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.