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

Daniel Fabian; Nianqiao Gong; Katrin Vogt; Hans Dieter Volk; Uwe Pleyer; Thomas Ritter

doi:10.1007/s00417-007-0629-y

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

Daniel Fabian, Nianqiao Gong, Katrin Vogt, Hans Dieter Volk, Uwe Pleyer, Thomas Ritter

Medicine

Charité – Universitätsmedizin Berlin

Research output: Contribution to a Journal (Peer & Non Peer) › Article › peer-review

12 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1515-1521
Number of pages	7
Journal	Graefe's Archive for Clinical and Experimental Ophthalmology
Volume	245
Issue number	10
DOIs	https://doi.org/10.1007/s00417-007-0629-y
Publication status	Published - Oct 2007

Keywords

Adenovirus
Cornea
Gene therapy
ICOSIg
Immunomodulation
Transplantation

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

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.",

keywords = "Adenovirus, Cornea, Gene therapy, ICOSIg, Immunomodulation, Transplantation",

author = "Daniel Fabian and Nianqiao Gong and Katrin Vogt and Volk, \{Hans Dieter\} and Uwe Pleyer and Thomas Ritter",

year = "2007",

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doi = "10.1007/s00417-007-0629-y",

language = "English",

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T1 - The influence of inducible costimulator fusion protein (ICOSIg) gene transfer on corneal allograft survival

AU - Fabian, Daniel

AU - Gong, Nianqiao

AU - Vogt, Katrin

AU - Volk, Hans Dieter

AU - Pleyer, Uwe

AU - Ritter, Thomas

PY - 2007/10

Y1 - 2007/10

N2 - 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.

AB - 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.

KW - Adenovirus

KW - Cornea

KW - Gene therapy

KW - ICOSIg

KW - Immunomodulation

KW - Transplantation

UR - https://www.scopus.com/pages/publications/34548720928

U2 - 10.1007/s00417-007-0629-y

DO - 10.1007/s00417-007-0629-y

M3 - Article

SN - 0721-832X

VL - 245

SP - 1515

EP - 1521

JO - Graefe's Archive for Clinical and Experimental Ophthalmology

JF - Graefe's Archive for Clinical and Experimental Ophthalmology

IS - 10

ER -

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

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