Challenges and opportunities in targeting the costimulation pathway in solid organ transplantation.

Flavio Vincenti, David Wojciechowski

Journal: Seminars in immunology 2012;23(3):157-64

PMID: 21856169

Full Text on Elsevier Science View on PubMed

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.

Address: University of California, San Francisco, Kidney Transplant Service, CA 94143-0780, United States. [email protected]

DOI: 10.1016/j.smim.2011.07.002

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MeSH Terms: Abatacept, CD28 Antigens, Graft Rejection, Humans, Immunoconjugates, Immunosuppression Therapy, Immunosuppressive Agents, Kidney Transplantation, Lymphocyte Activation, Organ Transplantation, Signal Transduction, T-Lymphocytes, Treatment Outcome