Fig. 2. Timeline for development of belatacept.
Blocking the CD28-CD80/CD86 costimulatory pathway has evolved from a mechanistic in vitro experimental tool to in vivo application for solid organ and islet transplantation, first in murine models and then in NHPs. In NHP transplant models, it was recognized that continuous therapy to prevent organ rejection would be more clinically useful than induction of tolerance and that a higher affinity molecule (belatacept) would be preferable to CTLA4-Ig. The FDA approved belatacept for kidney transplantation in 2010, 24 years after CTLA4-Ig was originally developed.