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Denise S Kim, Terry J Smith, Tünde Mester, Raymond S Douglas; The Effect of Teprotumumab (RV001) IGF-1 Receptor Blocking Antibody on Hematopoietic Cell Function: Implications for Graves' Orbitopathy. Invest. Ophthalmol. Vis. Sci. 2014;55(13):6305.
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© ARVO (1962-2015); The Authors (2016-present)
To assess the effect of teprotumumab (RV001), a highly specific human monoclonal antibody antagonist targeting IGF-1 receptor, on IGF-1R display on CD4+ T cells and CD14+ monocytes.
Peripheral blood mononuclear cells (PBMCs) were isolated from blood filters and fresh blood from healthy donors. PBMCs were incubated in medium with 1% fetal bovine serum without or with RV001 for 12, 24, or 48 hours. PBMCs were stained with tagged antibodies, washed, and fixed in 1% paraformaldehyde. They were analyzed by flow cytometry for IGF-1R display on CD4+ T cells and CD14+ monocytes.
RV001 decreased IGF-1R levels on CD4+ T cells (Fig. 1) and CD14+ monocytes (Fig. 2).
Our results demonstrate that RV001 decreases IGF-1R levels on CD4+ T cells and CD14+ monocytes from healthy donors. Previous studies have shown that IGF-1R might be an autoantigen in Graves' orbitopathy: activating anti-IGF-1R antibodies may promote cellular responses such as T and B cell migration and survival, and hyaluronan synthesis in orbital fibroblasts. Furthermore, IGF-1R and TSHR form a physical and functional complex. RV001 is a promising therapy that may be effective in mitigating Graves' orbitopathy by blocking the IGF-1R/TSHR inflammatory pathways.
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