title: Challenges and opportunities in targeting the costimulation pathway in solid organ transplantation.
abstract: Signaling through the costimulatory pathway is critical in the regulation of T cell activation. Abatacept, a selective costimulatory antagonist FDA approved for the treatment of moderate to severe rheumatoid arthritis, binds to CD80 and CD86 on antigen presenting cells, blocking the interaction with CD28 on T cells. Belatacept, a second generation CTLA4-Ig with 2 amino acid substitutions, has shown considerable promise in clinical transplantation as part of a maintenance immunosuppression regimen. This review will summarize the role of costimulation in T cell activation, detail the development of costimulation antagonists and highlight the pertinent clinical trials completed and ongoing utilizing belatacept as part of an immunosuppressive regimen in organ transplantation.
authors.affiliation: University of California, San Francisco, Kidney Transplant Service, CA 94143-0780, United States. david.wojciechowski@ucsf.edu
authors.forename: David
authors.initials: D
authors.lastname: Wojciechowski
authors.forename: Flavio
authors.initials: F
authors.lastname: Vincenti
mesh_terms: D000069594:Abatacept; D018106:CD28 Antigens / Q000037:antagonists & inhibitors / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D018796:Immunoconjugates / Q000494:pharmacology; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016030:Kidney Transplantation / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D016377:Organ Transplantation; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D018106:CD28 Antigens; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D000069594:Abatacept