Antiidiotype mAb:an Antiangiogenic /Antimetastatic Agent

抗独特型单克隆抗体：一种抗血管生成/抗转移剂

基本信息

批准号：
6485883
负责人：
FRANCIS S MARKLAND
金额：
$ 12.24万
依托单位：
PIVOTAL BIOSCIENCES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-03-01 至 2004-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6485883
关键词：
angiogenesis inhibitors antiidiotype antibody antineoplastics athymic mouse biotherapeutic agent human genetic material tag immunologic substance development /preparation laboratory mouse metastasis monoclonal antibody reptile poison

项目摘要

DESCRIPTION (provided by applicant): Angiogenesis (new blood vessel formation) is a critical step for tumor growth and metastasis, and its inhibition is currently the most promising approach for cancer therapy. Contortrostatin (ON) is a protein isolated from southern copperhead snake venom, which has been shown to effectively block angiogenesis, as well as metastasis. The potent inhibitory effect of CN on cancer progression has been proven in animal models of several types of cancer. However, two problems hinder its clinical application. First, ON is recognized by the human immune system as a foreign protein. Therefore, repetitive delivery of ON to patients induces the production of antibodies that neutralize its activity. Second, ON is eliminated from the circulation too quickly to exert a sustained effect. We propose to circumvent these obstacles by making an antibody to the ON antibody (antiidiotype) that will mimic the anti-cancer activity of native ON. This ON surrogate can then be genetically modified to resemble a human antibody (humanized), which will evade rejection by the immune system. The life span of this 'humanized" antibody in circulation will be similar to native immunoglobulin and thus ideal for long-term therapy. This project should result in a biopharmaceutical lead for antiangiogenic therapy. PROPOSED COMMERCIAL APPLICATION: In 1999, the NIH designated the development of antiangiogenic therapies for cancer as a national priority. About two dozen antiangiogenic drugs have entered clinical trials, and some cancer patients have experienced dramatic regression or stabilization of their tumor from antiangiogen therapy. Yet, none of these antiangiogenic drugs have been approved by FDA. According to the Angiogenesis Foundation, diseases that may be treatable with angiogenesis-based drugs encompass markets representing 20% of the $322 billion global pharmaceutical market.

描述（由申请人提供）：血管生成（新血管形成）是肿瘤生长和转移的关键步骤，其抑制作用是目前最有希望的癌症治疗方法。 Concontrostatin (ON) 是从南方铜头蛇毒液中分离出来的一种蛋白质，显示可以有效阻止血管生成以及转移。强效的 CN对癌症进展的抑制作用已在动物模型中得到证实的几种类型的癌症。然而，有两个问题阻碍了其临床应用应用。首先，ON被人体免疫系统识别为外来物质蛋白质。因此，向患者重复递送 ON 会导致产生中和其活性的抗体。二、ON被淘汰循环太快而无法发挥持续效果。我们建议通过制造 ON 抗体的抗体来规避这些障碍（抗独特型）将模仿天然 ON 的抗癌活性。这个开启然后可以对替代物进行基因改造，使其类似于人类抗体（人源化），这将逃避免疫系统的排斥。寿命为这种循环中的“人源化”抗体将与天然抗体相似免疫球蛋白，因此非常适合长期治疗。这个项目应该会产生抗血管生成疗法的生物制药领先者。拟议的商业应用： 1999年，美国国立卫生研究院将开发癌症抗血管生成疗法列为国家优先事项。大约有两打抗血管生成药物已进入临床试验，一些癌症患者的肿瘤在抗血管生成治疗中经历了戏剧性的消退或稳定。然而，这些抗血管生成药物均未获得 FDA 批准。据血管生成基金会称，可以用基于血管生成的药物治疗的疾病所涉及的市场占 3220 亿美元全球制药市场的 20%。