Developing Ligand/Receptor System with Infinite Affinity

描述（由申请人提供）： 开发将治疗剂靶向癌细胞的技术， 保留正常细胞是一种有希望的改进治疗的方法。 的 选择的特异性靶向试剂是单克隆抗体及其组合。 衍生物. 目前有一个很好的选择这样的分子，结合 高度表达的肿瘤抗原。 抗癌抗体Rituxan和 赫赛汀已被FDA批准用作治疗药物， 几种基于抗体的药物有望很快获得批准。 的 许多抗体与特征性癌抗原的结合亲和力 非常低;它们依赖于多价结合， 效用 出于这个原因，具有单一功能的工程化蛋白质的实用性是不可或缺的。 结合位点-如单链Fv分子或Fab片段-是有限的。 现代组合遗传技术的使用已经导致了以下方面的改进： 工程蛋白的抗原结合特性，但进一步的进展 是必要的。 我们提出了一种基因/化学相结合的方法， 将一种这样的配体/受体相互作用提高到特异性， 不可逆绑定。 这项研究将最终导致产品， 或者作为靶向治疗的第一步， 药物、放射性核素或其他效应物。 拟定商业应用： 用于药物递送的靶向选择性、不可逆结合平台，适用于靶向治疗、放射治疗、前药递送和其中优选长寿命特异性结合的其它应用。

DESCRIPTION (provided by applicant): Developing technology to target therapeutic agents to cancer cells, while sparing normal cells, is a promising approach to improved treatment. The specific targeting reagents of choice are monoclonal antibodies and their derivatives. Currently there is a good selection of such molecules that bind to highly expressed tumor antigens. The anticancer antibodies Rituxan and Herceptin have been approved by the FDA for use as therapeutic drugs, and several more antibody-based drugs are expected to be approved soon. The binding affinities of many antibodies to characteristic cancer antigens are strikingly low; they depend on multivalent binding for their practical utility. For this reason, the utility of engineered proteins with single binding sites-such as single chain Fv molecules or Fab fragments-is limited. The use of modern combinatorial genetic techniques has led to improvements in the antigen-binding properties of engineered proteins, but further advances are needed. We propose a combined genetic/chemical approach to radically improve one such ligand/receptor interaction to the point of specific, irreversible binding. This research will ultimately lead to products that are themselves therapeutic drugs, or that serve as the first step in targeting drugs, radionuclides, or other effectors, to sites of disease. PROPOSED COMMERCIAL APPLICATION: Target-selective, irreversibly bindig platform for drug delivery, suitable for use in targeted therapy, radiotherapy, prodrug delivery, and other applications where long-lived specific binding is preferred.