Improved diagnostic and monitoring assays for thyroid cancer

简介（申请人提供）：甲状腺癌是最常见的内分泌恶性肿瘤。每天都有新的甲状腺癌患者被发现，大多数患者在诊断后活了几十年。甲状腺癌患者的血清或细针活检中的甲状腺球蛋白（TG）水平通常使用各种机构批准的（如FDA）免疫测定法进行定量诊断和预后。事实上，量化TG水平的免疫分析是这些患者诊断和监测过程的金标准。人们会预期，这种经常规定的免疫测定将是高度可靠和容易解释的。不幸的是，事实并非如此。目前TG IVD免疫测定的局限性始于其构建所需的分析物。目前，TG必须从人体尸体或废弃的人体手术组织中获得。当从腺体匀浆中纯化蛋白质时，这会产生巨大的成本，并且供应商的批次差异问题可能相当大。此外，患者血清中抗TG自身抗体的存在会干扰这些检测及其解释。目前还没有办法解决这些问题或限制。在第二阶段的SBIR中，我们将继续努力为这两个问题提供新的解决方案。利用一种新的平台技术，我们成功地在转基因大豆种子中表达了全长人TG。据我们所知，这是重组人TG的唯一来源，也是使用任何蛋白质表达系统唯一成功表达该蛋白的方法。我们提出，这种可再生的TG来源将证明比甲状腺衍生的TG更均匀，更容易生产，更容易纯化。此外，我们建议构建一种可用于消除患者血清中干扰这些免疫测定的抗tg自身抗体的装置。如果成功，这些成就将显著提高目前设计用于诊断和监测甲状腺癌患者的TG免疫测定。

DESCRIPTION (provided by applicant): Thyroid cancer is the most common type of endocrine malignancy. New thyroid cancers patients are identified daily, and most patients live for decades following diagnosis. Thyroglobulin (TG) levels in the sera or in fine needle biopsies of thyroid cancer patients are routinely quantified using various agency- approved (e.g. FDA) immunoassays for diagnostic and prognostic purposes. In fact, immunoassays to quantify TG levels are the gold standard for the diagnosis and monitoring process for these patients. One would anticipate that such frequently prescribed immunoassays would be highly reliable and easily interpreted. Unfortunately, this is not the case. The limitations of present day TG IVD immunoassays begin with the analytes required for their construction. Presently, TG must be obtained from human cadavers or from discarded human surgical tissue. This creates significant costs when purifying the protein from gland homogenates, and the problem of lot to lot variation by supplier can be considerable. Furthermore, the presence of autoantibodies against TG in the sera of patients can interfere with these assays and their interpretation. Presently there is no solution to these problems or limitations. In this Phase II SBIR, we will continue our efforts to provide new solutions for both these problems. Using a novel platform technology, we have successfully expressed full length human TG in transgenic soybean seeds. To our knowledge, this is the only source of recombinant human TG, and is the only successful expression of this protein using any protein expression system. We propose that this renewable source of TG will prove to be more homogenous, easier to produce, and easier to purify than thyroid- derived TG. Further, we propose the construction of a device that can be used for the elimination of anti-TG autoantibodies from the sera of patients that can interfere with these immunoassays. If successful, these accomplishments should significantly enhance present day TG immunoassays designed to diagnose and monitor patients with thyroid cancers.