Alternatives to calcineurin inhibition in renal transplantation: belatacept, the first co-stimulation blocker.
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.
Poirier
Nicolas
N
INSERM, UMR643, Nantes F44093, France.
Blancho
Gilles
G
Vanhove
Bernard
B
D000069594:Abatacept; D000818:Animals; D018501:Antirheumatic Agents; D065095:Calcineurin Inhibitors; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D017277:Drug Approval; D055808:Drug Discovery; D006084:Graft Rejection / Q000188:drug therapy*; D006801:Humans; D018796:Immunoconjugates / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D007165:Immunosuppression Therapy; D016030:Kidney Transplantation; D008213:Lymphocyte Activation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology
D018501:Antirheumatic Agents; D065095:Calcineurin Inhibitors; D018796:Immunoconjugates; D000069594:Abatacept