Improved diagnostic and monitoring assays for thyroid cancer

改进甲状腺癌的诊断和监测分析

• 批准号: 8692671
• 负责人: KENNETH J PILLER
• 金额: $ 39.02万
• 依托单位: SOYMEDS, INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8692671
• 关键词: Autoantibodies; Biological Assay; Cadaver; Cancer Patient; Cancer Survivor; Clinical; Development; Devices; Diagnosis; Diagnostic; Diagnostic tests; Endocrine; FDA approved; Fine-needle biopsy; Gland; Goals; Gold; Guidelines; Human; Immunoassay; In Vitro; Industry; Label; Laboratories; Length; Life; Malignant Neoplasms; Malignant neoplasm of thyroid; Manufacturer Name; Marketing; Medical Device; Monitor; Notification; Operative Surgical Procedures; Patient Monitoring; Patients; Phase; Physicians; Plague; Process; Production; Property; Proteins; Reagent; Recombinants; Recurrence; Regulation; Sampling; Seeds; Serum; Small Business Innovation Research Grant; Solutions; Source; Soybeans; System; Technology; Thyroglobulin; Thyroglobulin antibody; Thyroid Gland; Time; Tissues; Transgenic Organisms; Variant; cost; design; diagnosis standard; improved; large scale production; novel; pathogen; performance tests; phase 1 study; prognostic; protein expression; public health relevance; screening; soy; transmission process; trend

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.

描述（由申请人提供）：甲状腺癌是最常见的内分泌恶性肿瘤。每天都会发现新的甲状腺癌患者，大多数患者在诊断后可以存活数十年。出于诊断和预后目的，通常使用各种经机构批准（例如 FDA）的免疫测定法对甲状腺癌患者血清或细针活检中的甲状腺球蛋白（TG）水平进行定量。事实上，量化 TG 水平的免疫测定是这些患者诊断和监测过程的金标准。人们预计这种经常使用的免疫测定方法将非常可靠且易于解释。不幸的是，事实并非如此。 当今 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，并且供应商的批次间差异问题可能会相当严重。此外，患者血清中存在抗 TG 自身抗体可能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。使用新颖的平台技术，我们已成功在转基因大豆种子中表达全长人类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成功表达该蛋白质的唯一来源。我们认为，这种可再生的 TG 来源将比甲状腺衍生的 TG 更均质、更容易生产、更容易纯化。此外，我们建议构建一种装置，可用于消除患者血清中可能干扰这些免疫测定的抗 TG 自身抗体。如果成功，这些成就将显着增强当今用于诊断和监测甲状腺癌患者的 TG 免疫测定。