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

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 x 10(9) 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.