Alternatives to calcineurin inhibition in renal transplantation: belatacept, the first co-stimulation blocker

Abstract

In the early 1990s, Linsley and colleagues produced a soluble fusion protein, comprising of the extracellular domain of cytotoxic T lymphocyte antigen (CTLA)4 and the human IgG1 Fc domain. Since then, several hundreds of scientific publications have demonstrated that CTLA4–Ig blocks CD28-mediated co-stimulation and suppresses unwanted T cell-mediated responses in animal models of transplantation, autoimmunity and inflammation. In the past two decades, Bristol-Myers Squibb Co. has developed abatacept, a CTLA4–Ig molecule for treating psoriasis and rheumatoid arthritis, and belatacept, a second-generation, higher affinity CTLA4–Ig molecule for use in kidney transplantation. Belatacept represents a new class of transplantation immunosuppressants and potentially offers clinicians a breakthrough therapy to preserve kidney function in the long term and reduce the side effects of current immunosuppressive therapies.