Novel insights into anti-CD40/CD154 immunotherapy in transplant tolerance.
Since the discovery of the CD40-CD154 costimulatory pathway and its critical role in the adaptive immune response, there has been considerable interest in therapeutically targeting this interaction with monoclonal antibodies in transplantation. Unfortunately, initial promise in animal models gave way to disappointment in clinical trials following a number of thromboembolic complications. However, recent mechanistic studies have identified the mechanism of these adverse events, as well as detailed a myriad of interactions between CD40 and CD154 on a wide variety of immune cell types and the critical role of this pathway in generating both humoral and cell-mediated alloreactive responses. This has led to resurgence in interest and the potential resurrection of anti-CD154 and anti-CD40 antibodies as clinically viable therapeutic options.
Emory Transplant Center, Emory University, Woodruff Memorial Research Building, 101 Woodruff Circle, Suite 5105, Atlanta, GA 30322, USA.
David F
DF
Pinelli
Mandy L
ML
Ford
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism*; D023201:CD40 Ligand / Q000276:immunology / Q000378:metabolism*; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008213:Lymphocyte Activation / Q000187:drug effects; D016377:Organ Transplantation; D020239:Receptor Cross-Talk / Q000187:drug effects; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D023001:Transplantation Tolerance / Q000187:drug effects
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D011948:Receptors, Antigen, T-Cell; D023201:CD40 Ligand
CD40; CD40L; Fc receptor; costimulation; thromboembolism; transplantation