Rational Development of LEA29Y (belatacept), a High-Affinity Variant of CTLA4-Ig with Potent Immunosuppressive Properties

Current success in organ transplantation is dependent upon the use of calcineurin-inhibitor-based im-munosuppressive regimens. Unfortunately, current immunotherapy targets molecules with ubiquitous ex-pression resulting in devastating non-immune side effects. T-cell costimulation has been identified as a new potential immunosuppressive target. The best characterized pathway includes CD28, its homologue CTLA4 and their ligands CD80 and CD86. While an im-munoglobulin fusion protein construct of CTLA4 sup-pressed rejection in rodents, it lacked efficacy in primate transplant models. In an attempt to increase the biologic potency of the parent molecule a novel, modified version of CTLA4-Ig, LEA29Y (belatacept),…

• NS
  National Science Foundation

  Award: 9731643
• CA
  Carlos and Marguerite Mason Trust
• NI
  National Institutes of Health

  Awards: RR00165, EEC-9731643, P51-RR00165