Antiidiotype mAb:an Antiangiogenic /Antimetastatic Agent

描述(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。Contortrostatin(打开) 是从南方铜鱼蛇毒中分离出来的一种蛋白质，它已经被 证明能有效地阻止血管生成以及转移。强大的 CN对肿瘤进展的抑制作用已在动物模型中得到证实 几种类型的癌症。然而，有两个问题阻碍了其临床应用。 申请。首先，ON是被人类免疫系统识别为异物的 蛋白。因此，重复地向患者传递ON会导致 产生中和其活性的抗体。第二，On被淘汰 从流通速度过快起到持续的作用。我们建议 通过制造针对On抗体的抗体来绕过这些障碍 (抗独特型)将模仿天然ON的抗癌活性。这是开着的 然后可以对代孕物进行基因改造，使其类似于人类抗体 (人性化)，这将避免免疫系统的排斥反应。人的生命周期 这种流通中的人源化抗体将类似于天然抗体 免疫球蛋白，因此是长期治疗的理想选择。这个项目应该会有结果 用于抗血管生成治疗的生物制药先导药物。 建议的商业应用： 1999年，美国国立卫生研究院将癌症抗血管生成疗法的开发列为国家优先事项。大约20多种抗血管生成药物已经进入临床试验，一些癌症患者的肿瘤在抗血管原治疗后经历了戏剧性的退化或稳定。然而，这些抗血管生成药物都没有得到FDA的批准。根据血管生成基金会的数据，可能可以用基于血管生成的药物治疗的疾病涵盖了占3220亿美元全球药品市场20%的市场。

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.