CTLA4Ig gene transfer prolongs survival and induces donor-specific tolerance in a rat renal allograft.
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.
Tomasoni
Susanna
S
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Azzollini
Nadia
N
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Casiraghi
Federica
F
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Capogrossi
Maurizio C
MC
Laboratory of Vascular Pathology, Istituto Dermopatico dell'Immacolata IDI-IRCCS, Rome, Italy.
Remuzzi
Giuseppe
G
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.|Division of Nephrology and Dialysis, Azienda Ospedaliera, Ospedali Riuniti di Bergamo, Bergamo, Italy.
Benigni
Ariela
A
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
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
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