BIOSYNTHESIS, GLYCOSYLATION, AND ACTION OF THYROTROPIN--CLINICAL TRIALS OF TSH

重组促甲状腺激素已经通过瞬时表达的新方法产生。 α和hTSH β小基因稳定转染中国人 仓鼠卵巢细胞 利用大规模生产的产品 生物反应器以及中空纤维生物反应器，我们已经能够 提纯几百毫克这种产品。 末端唾液酸化 重组促甲状腺激素的表达决定了其在体外和体内的生物活性 作为清除率。 重组TSH的糖结构具有 已被详细描述，并与垂体TSH不同。 通过与Genzyme的合作研发协议 公司（波士顿），重组人TSH被用于临床 甲状腺癌患者的研究。 该产品预计将 刺激放射性碘摄取， 治疗目的，并考虑到需要进行摄取 甲状腺功能减退症患者的研究。 研究新药申请 已获美国食品和药物管理局批准， 临床试验已经在NIH和其他4个医学中心完成 在19名患者中显示了初步疗效和安全性。 III期试验 在NIH和其他11个医疗中心，涉及100多名患者， 目前已接近完成。 目前，我们已经开发了第二个 第二代长效TSH类似物，其中嵌合β亚基具有 被设计了。

Recombinant thyrotropin has been produced by novel methods of transient or stable transfection of alpha and hTSH beta minigenes into Chinese hamster ovary cells. Utilizing products produced in a large scale bioreactor as well as a hollow fiber bioreactor, we have been able to purify several hundred milligrams of this product. Terminal sialylation of recombinant TSH determines in vitro and in vivo bioactivity as well as clearance rate. The carbohydrate structure of recombinant TSH has been characterized in detail and differs from pituitary TSH. Through a Cooperative Research and Development Agreement with the Genzyme Corporation (Boston), recombinant human TSH is being used for clinical studies in patients with thyroid cancer. This product is expected to stimulate uptake of radioactive iodine for both diagnostic and therapeutic purposes and to obviate the need for performing uptake studies in hypothyroid patients. An Investigational New Drug Application has been approved by the Food and Drug Administration and phase I and II clinical trials have been completed at NIH and 4 other medical center showing preliminary efficacy and safety in 19 patients. Phase III trials at NIH and 11 other medical centers involving over 100 patients are currently near completion. Currently we have developed a second generation long acting TSH analog in which a chimeric beta subunit has been engineered.