Chemically Programmed Antibodies for Cancer Therapy

用于癌症治疗的化学编程抗体

基本信息

批准号：
6823398
负责人：
CARLOS F BARBAS
金额：
$ 30.78万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-08-10 至 2009-07-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The study proposed here seeks to develop efficacious new therapeutic agents for the treatment of cancer. An increased understanding of molecular targets associated with tumor angiogenesis that supports cancer growth, receptors involved in cancer metastasis, and molecular targets associated with tumor cells themselves, provide novel opportunities for effective targeting of cancer at multiple levels. The promise of targeting antibodies to both the tumors vasculature and the tumor itself is a new and effective therapy for a variety of cancers. We hypothesize that the integrins avb3 and avb5 might fulfill some of these criteria. In preliminary studies, we have prepared a novel chemically programmed antibody that targets the integrins avb3 and avb5 and demonstrated the efficacy of this immunotherapeutic in animal models of Kaposi's sarcoma, melanoma, and colon cancer. Additionally, we have identified ligands that target several other tumor associated markers that can complement the integrin markers in providing a concerted molecular therapy for cancer. We hypothesize that antibodies that target tumor associated antigens as well as angiogenic receptors wilt be more potent and broadly applicable therapeutic agents. We will attempt to further validate the utility of our chemically programmed antibody approach and the dual compartment targeting hypothesis in animal models of cancer. Given the relevance of integrins avb3 and avb5 in melanoma, ovarian, and cervical cancers and in angiogenesis in general, success using these molecular targets and the chemically programmed antibody approach proposed herein may have many benefits. With chemically-programmed antibodies, we will address the therapeutic potential and mechanism of treating melanoma, breast, and ovarian cancer in animal models with single antibodies that target 1,2, or 3 defined receptors while addressing the question of whether there is a synergistic or additive advantage of combining anti-angiogenic and tumor targeted immunotherapies in cancer. It is anticipated that the results of this work will provide a promising new approach to the treatment of cancer.

描述（由申请人提供）：此处提出的研究旨在开发有效的新治疗剂来治疗癌症。对支持癌症生长，涉及癌症转移的受体以及与肿瘤细胞本身相关的分子靶标相关的分子靶靶标的分子靶靶标有了增加的理解，这为有效靶向多个水平的癌症提供了新的机会。针对肿瘤脉管系统和肿瘤本身的抗体的希望是对各种癌症的一种新的有效疗法。我们假设整联蛋白AVB3和AVB5可能满足其中一些标准。在初步研究中，我们制作了一种新型的化学程序化抗体，该抗体靶向整联蛋白AVB3和AVB5，并证明了这种免疫治疗性在Kaposi的肉瘤，黑色素瘤和结肠癌的动物模型中的功效。此外，我们已经确定了针对其他几种肿瘤相关标记的配体，这些配体可以补充整联蛋白标记在提供癌症的协同分子治疗时。我们假设靶向肿瘤相关抗原以及血管生成受体的抗体更有效，更广泛地适用治疗剂。我们将尝试进一步验证我们化学编程的抗体方法和靶向癌症动物模型中靶向假设的双室的效用。鉴于整联蛋白AVB3和AVB5在黑色素瘤，卵巢和宫颈癌中的相关性以及一般的血管生成中，使用这些分子靶标的成功，并且此处提出的化学程序化抗体方法可能具有许多好处。借助化学编程的抗体，我们将解决具有单一抗体的动物模型中治疗黑色素瘤，乳腺癌和卵巢癌的治疗潜力和机制，这些抗体的靶向1,2或3个定义的受体，同时解决了结合抗抗血管生成和肿瘤靶向免疫治疗的癌症中是否存在协同或添加性优势。预计这项工作的结果将为癌症治疗提供一种有希望的新方法。