title: CTLA4Ig gene transfer prolongs survival and induces donor-specific tolerance in a rat renal allograft.
abstract: Organ transplantation requires lifelong antirejection therapy, which carries the risk of infection and cancer. A revolutionary approach is to transduce the organ graft with immunomodulatory genes to render them tolerated with no need of systemic immunosuppression. Prolonged allograft survival was achieved by adenovirus-mediated transduction of the cold-preserved kidney with sequences encoding CTLA4Ig, a recombinant fusion protein that blocks T cell activation. Organ expression of the transgene was achieved associated with mild infiltration of mononuclear cells in the transfected kidney. Mixed lymphocyte reaction as well as the production of both Thl and Th2 cytokines were reduced. Thus, the gene transfer technique to prolong graft survival is indeed effective and safe and can induce donor-specific unresponsiveness. Pending appropriate large animal testing, ex vivo genetic manipulation of the organ before surgery may hopefully represent a major step forward in human transplant medicine.
authors.affiliation: Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
authors.forename: Susanna
authors.initials: S
authors.lastname: Tomasoni
authors.affiliation: Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Azzollini
authors.affiliation: Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Casiraghi
authors.affiliation: Laboratory of Vascular Pathology, Istituto Dermopatico dell'Immacolata IDI-IRCCS, Rome, Italy.
authors.forename: Maurizio C
authors.initials: MC
authors.lastname: Capogrossi
authors.affiliation: Mario Negri Institute for Pharmacological Research, Bergamo, Italy.|Division of Nephrology and Dialysis, Azienda Ospedaliera, Ospedali Riuniti di Bergamo, Bergamo, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
authors.affiliation: Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
authors.forename: Ariela
authors.initials: A
authors.lastname: Benigni
mesh_terms: D000069594:Abatacept; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000941:Antigens / Q000032:analysis; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D060908:CTLA-4 Antigen; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006085:Graft Survival; D007108:Immune Tolerance; D018796:Immunoconjugates; D007668:Kidney / Q000276:immunology / Q000473:pathology; D016030:Kidney Transplantation; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D009000:Monocytes / Q000473:pathology; D012313:RNA / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014019:Tissue Donors; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
chemical_list: D000941:Antigens; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556708:Ctla4 protein, rat; D018796:Immunoconjugates; D012313:RNA; D000069594:Abatacept