Improved diagnostic and monitoring assays for thyroid cancer

描述（由申请人提供）：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组织检查中的甲状腺球蛋白（TG）水平常规使用各种机构批准的（例如FDA）免疫测定法定量，用于诊断和预后目的。事实上，定量TG水平的免疫测定是这些患者诊断和监测过程的金标准。可以预期，这种频繁规定的免疫测定将是高度可靠和容易解释的。不幸的是，情况并非如此。 当前TG IVD免疫测定的局限性开始于其构建所需的分析物。目前，TG必须从人尸体或从丢弃的人手术组织中获得。当从腺体匀浆中纯化蛋白质时，这产生了显著的成本，并且供应商的批次间差异的问题可能是相当大的。此外，患者血清中抗TG自身抗体的存在会干扰这些测定及其解释。目前还没有解决这些问题或限制的方法。 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人TG。据我们所知，这是重组人TG的唯一来源，并且是使用任何蛋白表达系统成功表达该蛋白的唯一方法。我们认为，这种可再生来源的TG将被证明是更均匀，更容易生产，更容易纯化比甲状腺衍生的TG。此外，我们提出了一种装置的建设，可用于消除抗TG自身抗体从患者的血清中，可以干扰这些免疫测定。如果成功的话，这些成就将显著增强目前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.