Teprotumumab, an IGF-1R Blocking Monoclonal Antibody Inhibits TSH and IGF-1 Action in Fibrocytes

Context: Thyroid-associated ophthalmopathy (TAO) is the component of Graves' disease characterized by orbital inflammation and connective tissue remodeling. The IGF-1 receptor (IGF-1R) and TSH receptor (TSHR) form a physical and functional complex in orbital fibroblasts. A subset of these fibroblasts is derived from infiltrating CD34+ fibrocytes. Teprotumumab (RV 001, R1507) is a human monoclonal anti-IGF-1R blocking antibody currently undergoing a phase 2 clinical trial in patients with active TAO. Objective: To determine whether teprotumumab inhibits the induction by TSH of IL-6 and IL-8 in fibrocytes. Design: Fibrocytes were treated without or with teprotumumab in combination with IGF-1 or TSH. Main Outcome Measures: IL-6 and IL-8 mRNA expression and protein production were analyzed by real-time PCR and Luminex, respectively. Phosphorylated Akt (S473) levels were analyzed by Western blot. TSHR and IGF-1R display was assessed by flow cytometry. Results: Fibrocyte display of IGF-1R and TSHR was reduced w...