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

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.

► Costimulation pathways are involved in T cell regulation.
► Belatacept blocks an important costimulatory pathway (CD28:CD80/86).
► In transplantation belatacept has demonstrated significant renal preservation.
► Optimal use of belatacept is in a lower intensity regimen in EBV positive/low immunologic risk patients.