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.
Fabian
Daniel
D
Institute of Medical Immunology, Charité-University Medicine Berlin, Berlin, Germany.
Gong
Nianqiao
N
Vogt
Katrin
K
Volk
Hans-Dieter
HD
Pleyer
Uwe
U
Ritter
Thomas
T
D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics*; D003315:Cornea / Q000378:metabolism*; D016039:Corneal Transplantation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006085:Graft Survival / Q000502:physiology*; D007074:Immunoglobulin G / Q000235:genetics; D060889:Inducible T-Cell Co-Stimulator Protein; D009924:Organ Culture Techniques; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D011993:Recombinant Fusion Proteins / Q000235:genetics; D014184:Transplantation, Homologous
D000914:Antibodies, Viral; D000945:Antigens, Differentiation, T-Lymphocyte; C556695:Icos protein, rat; D007074:Immunoglobulin G; D060889:Inducible T-Cell Co-Stimulator Protein; D011993:Recombinant Fusion Proteins