SBIR-STTR Award

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.

Thesaurus Terms:
Address;Affinity;Assay;Au Element;Autoantibodies;Binding;Binding (Molecular Function);Bioassay;Biologic Assays;Biological Assay;Blood Serum;Body Tissues;Cadaver;Cancer Patient;Cancer Survivor;Cancerous;Cancers;Cells;Clinical;Diagnosis;Diagnostic;Diagnostic Tests;Endocrine;Fda Approved;Gold;Head And Neck, Thyroid;Heterogeneity;Human;Human, General;Immunoassay;Knowledge;Laboratories;Length;Malignant;Malignant - Descriptor;Malignant Neoplasms;Malignant Thyroid Gland Neoplasm;Malignant Tumor;Malignant Tumor Of The Thyroid;Malignant Tumor Of The Thyroid Gland;Malignant Neoplasm Of Thyroid;Man (Taxonomy);Man, Modern;Measurement;Medical Device;Metastasis;Metastasize;Metastatic Neoplasm;Metastatic Tumor;Molecular Interaction;Monitor;Neoplasm Metastasis;Patient Monitoring;Patients;Phase;Physicians;Plague;Plant Embryos;Proteins;Sbir;Sbirs (R43/44);Sampling;Secondary Neoplasm;Secondary Tumor;Seeds;Serum;Small Business Innovation Research;Small Business Innovation Research Grant;Solutions;Source;Soy Beans;Soybeans;Technology;Thyroglobulin;Thyroglobulin Antibody;Thyroid;Thyroid Cancer;Thyroid Gland;Thyroid Gland Hormone;Thyroid Hormones;Time;Tissues;Transgenic Organisms;Transmission;Tumor Cell Migration;Yersinia Pestis Disease;Zygotes, Plant;Anti-Thyroglobulin;Anti-Thyroglobulin Antibody;Antithyroglobulin;Autoimmune Antibody;Cancer Metastasis;Cost;Design;Designing;Gene Product;Improved;Malignancy;Neoplasm/Cancer;Novel;Pathogen;Prototype;Public Health Relevance;Seed;Self Reactive Antibody;Tool;Transgenic;Transmission Process

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.

Public Health Relevance Statement:


Public Health Relevance:
In this Phase II SBIR, we will continue our efforts to solve two of the most significant problems plaguing FDA-approved thyroglobulin (TG) immunoassays. Expressing full length human TG in transgenic soybean seeds provides a renewable source of this analyte which has properties superior to the variability seen with lots of protein purified frm thyroid tissues. Furthermore, the unique advantages of transgenic soybean-derived proteins will allow, for the first time, a practical solution for the elimination of anti-TG autoantibodies that an interfere with immunoassays. These accomplishments should significantly enhance present day TG immunoassays designed to diagnose and monitor patients with thyroid cancers.

Project Terms:
Autoantibodies; Biological Assay; Cadaver; Cancer Patient; Cancer Survivor; Clinical; cost; design; Development; Devices; Diagnosis; diagnosis standard; Diagnostic; Diagnostic tests; Endocrine; FDA approved; Fine-needle biopsy; Gland; Goals; Gold; Guidelines; Human; Immunoassay; improved; In Vitro; Industry; Label; Laboratories; large scale production; Length; Life; Malignant neoplasm of thyroid; Malignant Neoplasms; Manufacturer Name; Marketing; Medical Device; Monitor; Notification; novel; Operative Surgical Procedures; pathogen; Patient Monitoring; Patients; performance tests; Phase; phase 1 study; Physicians; Plague; Process; Production; prognostic; Property; protein expression; Proteins; public health relevance; Reagent; Recombinants; Recurrence; Regulation; Sampling; screening; Seeds; Serum; Small Business Innovation Research Grant; Solutions; Source; soy; Soybeans; System; Technology; Thyroglobulin; Thyroglobulin antibody; Thyroid Gland; Time; Tissues; Transgenic Organisms; transmission process; trend; Variant