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.
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.