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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，目前最有前途的癌症治疗方法。康托他汀（ON）是一种从南方铜斑蛇毒液中分离出来的蛋白质，显示出有效地阻断血管生成以及转移。强效 CN对癌症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，两个问题阻碍了其临床应用应用程序.首先，ON被人体免疫系统识别为外来物，蛋白因此，向患者重复递送ON诱导了肿瘤细胞的增殖。产生中和其活性的抗体。第二，ON被淘汰从血液循环中快速排出而无法产生持续的效果我们建议通过制造针对ON抗体的抗体来规避这些障碍（抗独特型），其将模拟天然ON的抗癌活性。然后可以对替代物进行遗传修饰以类似于人抗体（人源化的），其将逃避免疫系统的排斥。的寿命循环中的这种“人源化”抗体将类似于天然的免疫球蛋白，因此是长期治疗的理想选择。该项目将导致在抗血管生成治疗的生物制药领域领先。拟定商业应用： 1999年，NIH将开发癌症的抗血管生成疗法指定为国家优先事项。大约有24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已经从抗血管生成治疗中显著消退或稳定。然而，这些抗血管生成药物都没有被FDA批准。根据血管生成基金会的数据，可以用基于血管生成的药物治疗的疾病涵盖了占3220亿美元全球制药市场20%的市场。