Combination therapy with anti-ICOS and cyclosporine enhances cardiac but not islet allograft survival

• Published in: Transplantation proceedings Vol. 35; no. 7; pp. 2477 - 2478
• Main Authors: Nanji, S.A, Hancock, W.W, Anderson, C.C, Zhu, L.F, Kneteman, N.M, Shapiro, A.M.J
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New York, NY Elsevier Inc 01.11.2003; Elsevier Science
• Subjects: Animals; Antibodies, Monoclonal - therapeutic use; Biological and medical sciences; CD28 Antigens - immunology; Cyclosporine - therapeutic use; Drug Therapy, Combination; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Graft Survival - drug effects; Graft Survival - immunology; Heart Transplantation - immunology; Heart Transplantation - mortality; Immunomodulators; Immunosuppressive Agents - therapeutic use; Islets of Langerhans Transplantation - immunology; Islets of Langerhans Transplantation - mortality; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Models, Animal; Pharmacology. Drug treatments; Time Factors; Tissue, organ and graft immunology; Transplantation, Heterotopic; Transplantation, Homologous; Heart; Drug combination; Prognosis; Antibody; Rodentia; Langerhans islet; Homograft; Transplantation; Homotransplantation; Costimulatory molecule; Survival; Vertebrata; Chemotherapy; Mammalia; Mouse; Surgery; Animal; Immunotherapy; Graft; Ciclosporin; Combined treatment; Circulatory system; Immunosuppressive agent; Endocrine pancreas
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2003.08.029

The blockade of costimulatory signals is a powerful strategy to prevent allograft rejection and facilitate transplantation tolerance. In recent years, a series of novel costimulatory molecules have been identified, including an inducible costimulatory molecule (ICOS). To date, little has been uncovered regarding the therapeutic potential of blocking ICOS signaling in the setting of transplantation. In a fully MHC-mismatched mouse model, we studied the effect of blocking ICOS signaling using a specific monoclonal antibody (anti-ICOS mAb) in combination with cyclosporine on cardiac and islet allograft survival. We demonstrated that combined treatment with anti-ICOS mAb and cyclosporine can induce long-term graft acceptance in cardiac but not islet allografts, suggesting that the type of transplanted tissue significantly influences the immunologic patterns of graft acceptance or rejection in this model.