Improved diagnostic and monitoring assays for thyroid cancer

描述(申请人提供)：甲状腺癌是最常见的内分泌恶性肿瘤类型。每天都会发现新的甲状腺癌患者，大多数患者在确诊后可以活几十年。甲状腺癌患者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(例如FDA)免疫分析进行定量，以用于诊断和预后目的。事实上，定量测定甘油三酯水平的免疫分析是对这些患者进行诊断和监测过程的金标准。人们可以预料到，这种频繁开出的免疫分析将是高度可靠和容易解释的。不幸的是，情况并非如此。目前TG-IVD免疫分析的局限性始于其构建所需的分析物。目前，TG必须从人类身体或被丢弃的人类手术组织中获得。当从腺体匀浆中提纯蛋白质时，这会产生很大的成本，而且供应商之间的批次差异可能会很大。此外，患者血清中抗甘油三酯自身抗体的存在可能会干扰这些检测及其解释。目前还没有解决这些问题或限制的办法。在第二阶段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的人TG。据我们所知，这是重组人TG的唯一来源，也是唯一使用任何蛋白质表达系统成功表达该蛋白的来源。我们认为，这种可再生来源的甘油三酯将被证明比甲状腺来源的甘油三酯更均匀，更容易生产，更容易纯化。此外，我们建议构建一种设备，用于消除患者血清中可能干扰这些免疫分析的抗TG自身抗体。如果成功，这些成果将大大提高目前用于诊断和监测甲状腺癌患者的甘油三酯免疫分析。

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.