Costimulation blockade in autoimmunity and transplantation.
Signaling through the costimulation receptors is a critical pathway in the regulation of T-cell activation. The selective costimulation inhibitor abatacept (cytotoxic T lymphocyte-associated antigen 4-Ig) binds to CD80 and CD86 on antigen-presenting cells, blocking interaction with CD28 on T cells, and is approved for the treatment of moderate to severe rheumatoid arthritis. Belatacept (LEA29Y), currently enrolling phase III trials in renal transplantation, was rationally designed from abatacept to bind with more avidity to CD86, providing the more potent immunosuppressive properties required for immunosuppression in transplantation. This review describes the relevant preclinical studies and summarizes recent clinical findings on these 2 molecules in autoimmune diseases and organ transplantation. Although both inhibit the CD28 costimulatory pathway, they are tailored for specific disease states--abatacept for autoimmune diseases and belatacept for transplantation.
Vincenti
Flavio
F
University of California, San Francisco, Kidney Transplant Service, San Francisco, CA 94143-0780, USA. vincentif@surgery.ucsf.edu
D000069594:Abatacept; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D001327:Autoimmune Diseases / Q000188:drug therapy; D015551:Autoimmunity / Q000187:drug effects*; D018106:CD28 Antigens / Q000378:metabolism; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008024:Ligands; D016377:Organ Transplantation; D015398:Signal Transduction / Q000187:drug effects; D014181:Transplantation Immunology / Q000187:drug effects*
D018106:CD28 Antigens; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D008024:Ligands; D000069594:Abatacept