Costimulatory blockade with belatacept in clinical and experimental transplantation - a review

Current maintenance immunosuppression agents have been critical to the improved graft and patient survival rates in solid organ transplantation observed over the past decade. However, long-term follow-up has revealed that these agents are associated with troublesome side effects and chronic toxicity, contributing to graft loss and death.

Costimulation blockade has long been recognized as an important target for immunomodulation in solid organ transplantation. Belatacept, a high-affinity chimeric fusion protein that binds to CD80/CD86 on antigen-presenting cells, has shown great promise in renal transplantation and is now in Phase III trials.

This review explores the development and efficacy of belatacept, compared with currently approved immunosuppressive agents used in transplantation.

Belatacept seems to be an effective alternative to current maintenance immunosuppressive therapies, with no apparent end organ toxicity and a minimal side-effect profile. This agent works best when used in combination with therapies that target different pathways of T-cell activation, but the optimal regimen has not yet been identified. Data generated in ongoing clinical trials will be essential in validating previous studies and for further development of belatacept-based combinatorial strategies.