Type I Collagen as an Anti-Tumor Target

I 型胶原蛋白作为抗肿瘤靶点

• 批准号: 6334143
• 负责人: DANIEL L BROEK
• 金额: $ 10万
• 依托单位: CELL-MATRIX, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-06 至 2002-07-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6334143
• 关键词: angiogenesis inhibitors; antineoplastics; chorioallantoic membrane; collagen; drug design /synthesis /production; immunologic substance development /preparation; monoclonal antibody; neoplasm /cancer blood supply; neoplasm /cancer immunotherapy

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.

描述：（由申请人提供） 许多疾病的病理发生都需要血管的发育。 状态，包括癌症、血管性眼病和关节炎。一个新的目标 （即I型胶原蛋白）抑制新血管的发育 CMls 创始人之一的工作提出了这一点。申请目的 识别拮抗剂（以单克隆抗体的形式） 专门识别暴露的 I 型胶原蛋白中的隐秘位点 在血管形成的过程中。这些单克隆抗体将成为拮抗剂 针对完成所需的神秘监管站点 血管生成。这些单克隆抗体和其他结合同一位点的拮抗剂 可能是有效的血管生成抑制剂，并将有应用 治疗癌症和其他疾病。因为这些神秘的I型站点 胶原蛋白主要暴露在血管生成组织中，这些 Mab 将 可用于诊断癌症和其他疾病。三个具体目标是 建议：目标 1：识别一组可发生反应的单克隆抗体 (Mab) 含有变性但非天然的 I 型胶原蛋白。目标 2：测试效果 与内皮和肿瘤上变性的 I 型胶原蛋白发生反应的 Mab 体外细胞行为。目标 3：在小鸡中测试目标 1 中分离的单克隆抗体 绒毛尿囊膜 (CAM) 血管生成测定用于抗血管生成 活动。 拟议的商业应用： I 型胶原蛋白中隐藏位点的拮抗剂，可阻止血管生成和肿瘤生长 具有商业应用作为癌症和其他疾病的治疗和诊断 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 每年20亿美元。 根据该提案开发的产品可以捕获 这些销售额的很大一部分。