April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
The Effect of Teprotumumab (RV001) IGF-1 Receptor Blocking Antibody on Hematopoietic Cell Function: Implications for Graves' Orbitopathy
Author Affiliations & Notes
  • Denise S Kim
    Department of Ophthalmology and Visual Sciences, University of Michigan Medical School, Kellogg Eye Center, Ann Arbor, MI
  • Terry J Smith
    Department of Ophthalmology and Visual Sciences, University of Michigan Medical School, Kellogg Eye Center, Ann Arbor, MI
    Department of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan Medical School, Ann Arbor, MI
  • Tünde Mester
    Department of Ophthalmology and Visual Sciences, University of Michigan Medical School, Kellogg Eye Center, Ann Arbor, MI
  • Raymond S Douglas
    Department of Ophthalmology and Visual Sciences, University of Michigan Medical School, Kellogg Eye Center, Ann Arbor, MI
    Ann Arbor Veterans Administration Medical Center, Ann Arbor, MI
  • Footnotes
    Commercial Relationships Denise Kim, None; Terry Smith, 6,936,426 (P), 7,998,681 (P), 8,153,121 (P), 8,178,304 (P), River Vision LLC (C); Tünde Mester, None; Raymond Douglas, 8,178,304 (P), River Vision LLC (C)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 6305. doi:
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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)

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Abstract
 
Purpose
 

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.

 
Methods
 

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.

 
Results
 

RV001 decreased IGF-1R levels on CD4+ T cells (Fig. 1) and CD14+ monocytes (Fig. 2).

 
Conclusions
 

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.

 
 
Figure 1. RV001 reduces IGF-1R levels on CD4+ T cells. Histograms of flow cytometric analysis show IGF-1R levels on T cells (black line) compared to isotype control (gray-filled histogram). Addition of RV001 50 µg/ml (blue line) or 500 µg/ml (red line) reduced IGF-1R levels after 48 hours. The table shows the corresponding IGF-1R mean fluorescence intensity (MFI) in untreated and RV001-treated cells at 12, 24, and 48 hours.
 
Figure 1. RV001 reduces IGF-1R levels on CD4+ T cells. Histograms of flow cytometric analysis show IGF-1R levels on T cells (black line) compared to isotype control (gray-filled histogram). Addition of RV001 50 µg/ml (blue line) or 500 µg/ml (red line) reduced IGF-1R levels after 48 hours. The table shows the corresponding IGF-1R mean fluorescence intensity (MFI) in untreated and RV001-treated cells at 12, 24, and 48 hours.
 
 
Figure 2. RV001 reduces IGF-1R levels on CD14+ monocytes. Histograms of flow cytometric analysis show IGF-1R levels on monocytes (black line) compared to isotype control (gray-filled histogram). Addition of RV001 50 µg/ml (blue line) or 500 µg/ml (red line) reduced IGF-1R levels after 24 hours. The table shows the corresponding IGF-1R mean fluorescence intensity (MFI) in untreated and RV001-treated cells at 12, 24, and 48 hours.
 
Figure 2. RV001 reduces IGF-1R levels on CD14+ monocytes. Histograms of flow cytometric analysis show IGF-1R levels on monocytes (black line) compared to isotype control (gray-filled histogram). Addition of RV001 50 µg/ml (blue line) or 500 µg/ml (red line) reduced IGF-1R levels after 24 hours. The table shows the corresponding IGF-1R mean fluorescence intensity (MFI) in untreated and RV001-treated cells at 12, 24, and 48 hours.
 
Keywords: 543 growth factors/growth factor receptors • 555 immunomodulation/immunoregulation • 467 clinical laboratory testing  
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