June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Aflibercept (Eylea) inhibits dendritic cell migration
Author Affiliations & Notes
  • Matthias Hamdorf
    Cornea Lab Experimental Ophthalmology, University Hospital of Cologne, Cologne, Germany
    Terasaki Institute for Biomedical Innovation (TIBI), Los Angeles, California, United States
  • Jasmin Weindler
    Cornea Lab Experimental Ophthalmology, University Hospital of Cologne, Cologne, Germany
  • Ann-Charlott Salabaria
    Cornea Lab Experimental Ophthalmology, University Hospital of Cologne, Cologne, Germany
  • Claus Cursiefen
    Zentrum für Augenheilkunde - Department of Ophthalmology, Universitat zu Koln, Koln, Nordrhein-Westfalen, Germany
  • Felix Bock
    Cornea Lab Experimental Ophthalmology, University Hospital of Cologne, Cologne, Germany
  • Footnotes
    Commercial Relationships   Matthias Hamdorf None; Jasmin Weindler None; Ann-Charlott Salabaria None; Claus Cursiefen None; Felix Bock None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 907 – A0271. doi:
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    • Get Citation

      Matthias Hamdorf, Jasmin Weindler, Ann-Charlott Salabaria, Claus Cursiefen, Felix Bock; Aflibercept (Eylea) inhibits dendritic cell migration. Invest. Ophthalmol. Vis. Sci. 2022;63(7):907 – A0271.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The potential to control vascular endothelial growth factor (VEGF) induced intracellular signaling by targeting this cytokine offers promising therapeutic potential for vascular diseases and cancer. VEGF-A regulates angiogenesis but modulates the immune microenvironment. Dendritic cells are one of the responsible cell types that orchestrate the immune response in a transplant setting. Modulation of DCs by VEGF-A -trap (Aflibercept) might benefit in reduced inflammation and subsequent transplant survival. In this study, we analyzed the effect of Aflibercept and combinations of VEGF-A bound to Aflibercept on dendritic cells and possible positive effects on the immune system and graft survival.

Methods : Human monocytes were treated with Aflibercept during differentiation, and the expression of surface and activation markers were analyzed. Biological differences of treated cells were determined in a transwell migration assay. To verify the findings in human cell culture, we confirmed them in a murine model of suture-induced neovascularization and subsequent high-risk corneal transplantation. Mice were treated with VEGFR1/R2 trap before transplantation. We analyzed transplant integrity, CD11c+ dendritic cells, and tolerance marker 2 and 8 weeks later.

Results : The treatment of monocytes, with a combination of VEGF-A and Aflibercept during differentiation to DCs leads to an down regulation of MHC II and costimulatory markers on dendritic cells. Furthermore, the frequency of VEGFR1-positive cells increased significantly. As a functional outcome we found that in the presence of VEGF-A and Aflibercept the migration of mature DC was inhibited by aproximatly 50 %. To characterize this results more in details we went into the mouse model and local VEGFR1/R2 trap treatment significantly inhibits the infiltration of CD11c+ dendritic cells into the cornea. Subsequent increased corneal transplantation success was accompanied by a local upregulation of Foxp3 gene expression.

Conclusions : This study demonstrates that the application of Aflibercept modulates the differentiation and migration ability of dendritic cells and contributes to increased transplantation success and less inflammation mediated by DCs in a mouse cornea transplantation model.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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