Improved diagnostic and monitoring assays for thyroid cancer

描述（由申请方提供）：使用各种机构批准的（例如FDA）免疫测定法对甲状腺癌患者血清中的甲状腺球蛋白水平进行常规定量。医生经常使用这些诊断性免疫测定法来确定患者的甲状腺球蛋白水平。因此，毫不奇怪，许多不同的公司已经开发出自己的诊断测试用于购买和在临床实验室中使用。尽管目前有许多甲状腺球蛋白免疫测定法，但每一种都有其固有的局限性。事实上，不可能准确地比较从一种甲状腺球蛋白免疫测定法获得的结果与从另一种甲状腺球蛋白免疫测定法获得的结果。有两个主要问题需要解决。首先，缺乏一个普遍一致的甲状腺球蛋白标准显着的差异，FDA批准的免疫测定由不同的供应商。目前，作为免疫测定标准品的人甲状腺球蛋白的唯一来源来自尸体或手术切除的人甲状腺组织。不同批次人源性甲状腺球蛋白的异质性是一个尚未解决的局限性。其次，一些甲状腺癌患者血清中存在的抗甲状腺球蛋白自身抗体会干扰试图检测和定量甲状腺球蛋白的免疫测定。目前，这两个难题都没有明确的解决办法。 在本I期SBIR中，我们建议通过在转基因大豆种子中表达人甲状腺球蛋白作为II类医疗器械分析物，解决FDA批准的甲状腺球蛋白免疫测定法中两个最重要的问题。利用这种表达甲状腺球蛋白的新平台，我们可以生产出高度同质的免疫测定标准品。此外，转基因大豆衍生蛋白的独特优势（例如，同质性、易于纯化、非常低的成本、消除人类病原体传播、可再生的“绿色技术”等）也将被广泛应用。将允许，第一次，一个实用的解决方案，消除抗甲状腺球蛋白自身抗体，可以干扰免疫测定。这些成就将大大增强目前用于诊断和监测甲状腺癌患者的甲状腺球蛋白免疫测定。 公共卫生相关性：在本I期SBIR中，我们建议通过在转基因大豆种子中表达人甲状腺球蛋白作为II类医疗器械分析物来解决FDA批准的甲状腺球蛋白免疫测定法中两个最重要的问题。利用这种表达甲状腺球蛋白的新平台，我们可以生产出高度同质的免疫测定标准品。此外，这将为消除可能干扰免疫测定的抗甲状腺球蛋白自身抗体提供一种实用的解决方案。这些成就将大大增强目前用于诊断和监测甲状腺癌患者的甲状腺球蛋白免疫测定。

DESCRIPTION (provided by applicant): Thyroglobulin levels in the sera of thyroid cancer patients are routinely quantified using various agency-approved (e.g. FDA) immunoassays. Physicians frequently order these diagnostic immunoassays to determine thyroglobulin levels in their patients. Therefore it is not surprising that many different companies have developed their own diagnostic tests for purchase and use in the clinical laboratory. Despite the current availability of these numerous thyroglobulin immunoassays, each suffers from inherent limitations. In fact, it is not possible to accurately compare the results obtained from one thyroglobulin immunoassay with those obtained by another. There are two major problems which need to be solved. First, the lack of a universally consistent thyroglobulin standard contributes significantly to variability between FDA-approved immunoassays made by different suppliers. Presently, the only source of human thyroglobulin for use as a standard in immunoassays comes from cadavers or surgically removed human thyroid tissue. The heterogeneity of different lots of human-derived thyroglobulin is a limitation which has not been solved. Second, anti-thyroglobulin autoantibodies present in some thyroid cancer patients' sera can interfere with immunoassays that attempt to detect and quantify thyroglobulin. Currently, there are no clear solutions to either of these dilemmas. In this Phase I SBIR, we propose to solve two of the most significant problems plaguing FDA-approved thyroglobulin immunoassays by expressing human thyroglobulin in transgenic soybean seeds for use as a class II medical device analyte. Taking advantage of this novel platform for expressing thyroglobulin should allow us to produce a highly homogenous standard for immunoassays. Furthermore, the unique advantages of transgenic soybean-derived proteins (e.g. homogeneity, ease of purification, very low cost, elimination of human pathogen transmission, renewable "green technology", etc.) will allow, for the first time, a practical solution for the elimination of anti-thyroglobulin autoantibodies that can interfere with immunoassays. These accomplishments should significantly enhance present day thyroglobulin immunoassays designed to diagnose and monitor patients with thyroid cancers. PUBLIC HEALTH RELEVANCE: In this Phase I SBIR, we propose to solve two of the most significant problems plaguing FDA-approved thyroglobulin immunoassays by expressing human thyroglobulin in transgenic soybean seeds for use as a class II medical device analyte. Taking advantage of this novel platform for expressing thyroglobulin should allow us to produce a highly homogenous standard for immunoassays. Furthermore, this will allow a practical solution for the elimination of anti-thyroglobulin autoantibodies that can interfere with immunoassays. These accomplishments should significantly enhance present day thyroglobulin immunoassays designed to diagnose and monitor patients with thyroid cancers.