6723 Development and Validation of Long-Acting Recombinant Human Thyroid-Stimulating Hormone Using SAFA Technology

Abstract Disclosure: D. Kim: None. M. Kang: None. S. Lee: None. Y. Cho: None. G. Zi: Employee; Self; AprilBio Co. J. An: Employee; Self; AprilBio Co. J. Han: Employee; Self; AprilBio Co. S. Chi: Employee; Self; AprilBio Co. S. Cha: Owner/Co-Owner; Self; AprilBio Co.. E. Lee: None. Thyrogen, a recombinant human thyroid-stimulating hormone (rhTSH), has been useful in improving diagnostic radioiodine scanning and thyroglobulin testing for patients with thyroid cancer. It is also used with radioiodine therapy to eliminate remaining thyroid tissue. However, its short half-life in the bloodstream necessitates multiple doses during treatment. We developed a new long-acting rhTSH using anti-serum albumin Fab-associated (SAFA) technology. SAFA-TSH was produced using a Chinese hamster ovary expression system. To verify its biological activity, we generated Nthy-ori 3-1 cells stably overexpressing TSHR and measured the production of cAMP. In a rat study, slow-release T3 pellets were implanted three days prior to the administration of Thyrogen or SAFA-TSH, allowing for measurement of only the amount of T4 release resulting from exogenous administration. SAFA-TSH increased cAMP production dose-dependently, but less effectively than Thyrogen at similar concentrations. SAFA-TSH required 5∼6 times the dose of Thyrogen to achieve similar cAMP levels, likely due to steric hindrance from the TSH fusion to SAFA. In a rat study, SAFA-TSH produced elevated T4 levels well after the decline in the response to Thyrogen. SAFA-TSH had significantly higher cumulative effects on T4 and free T4 levels compared to Thyrogen, as observed by nearly 2-fold higher average area under the effect curve of 335.73 vs 192.06 μg×h/dL and 135.24 vs 68.52 μg×h/dL, respectively. Long-acting TSH with bioactivity was successfully created using SAFA technology. These data support further development of SAFA-TSH in a clinical setting, potentially representing an important advancement in the treatment of patients with thyroid cancer. Presentation: 6/3/2024