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The influence of inducible costimulator fusion protein (ICOSIg) gene transfer on corneal allograft survival

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Abstract

Background

The purpose of this paper is to analyse the effects of local or systemic administration of adenovirus type 5 encoding the inducible costimulator fusion protein (AdICOSIg) on its influence on prolonging corneal allograft survival.

Methods

The ICOSIg chimeric molecule was generated by fusing the murine ICOS to a rat FcIgG portion and a recombinant adenovirus (Ad) was made thereof. A major histocompatibility complex (MHC) class I/II mismatched rat corneal transplant model was used. The recipients were randomly assigned to receive ex vivo gene-modified corneas expressing either ICOSIg or a single i.p. injection (1.0 × 109 infectious particles) of AdICOSIg two days after transplantation and graft survival was analysed. Moreover, the influence of ICOSIg fusion protein on anti-adenovirus immunity also was investigated.

Results

The ex vivo gene transfer of ICOSIg in cultured corneas resulted in high levels of ICOSIg protein in culture supernatants. However, neither ex vivo nor systemic gene therapy resulted in a significant prolongation of graft survival. Interestingly, the generation of anti-adenovirus antibodies could not be inhibited by systemic ICOSIg fusion protein expression.

Conclusions

Unlike CTLA4Ig, sole ICOSIg gene therapy is not a successful strategy for the prevention of allogeneic graft rejection in corneal transplantation.

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Acknowledgements

The authors would like to thank Drs. H.W. Mages and R. Kroczek, Robert Koch Institute, Department of Immunology, Berlin, Germany, for providing the murine ICOSIg cDNA and the rat IgG cDNA expression cassette. Moreover, the authors are grateful to Mr. Heinz Tanzmann for his technical assistance. This work was supported in part by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) (Ri 764/10-1 and Pl 150/14-1).

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Authors and Affiliations

  1. Institute of Medical Immunology, Charité—University Medicine Berlin, Berlin, Germany

    Daniel Fabian, Katrin Vogt, Hans-Dieter Volk & Thomas Ritter

  2. Department of Ophthalmology, Charité—University Medicine Berlin, Berlin, Germany

    Nianqiao Gong & Uwe Pleyer

  3. Regenerative Medicine Institute (REMEDI), National Centre for Biomedical Engineering Science (NCBES), National University of Ireland, Galway, Ireland

    Thomas Ritter

Authors
  1. Daniel Fabian
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  2. Nianqiao Gong
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  4. Hans-Dieter Volk
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Corresponding author

Correspondence to Thomas Ritter.

Additional information

Daniel Fabian and Nianqiao Gong contributed equally to the manuscript.

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Fabian, D., Gong, N., Vogt, K. et al. The influence of inducible costimulator fusion protein (ICOSIg) gene transfer on corneal allograft survival. Graefes Arch Clin Exp Ophthalmol 245, 1515–1521 (2007). https://doi.org/10.1007/s00417-007-0629-y

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  • DOI: https://doi.org/10.1007/s00417-007-0629-y

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