Therapeutics: CD40 ligand (CD40L; CD40LG; CD154); CTLA-4 (CD152);

Mouse studies suggest inhibiting T cell co-stimulatory pathways could help prevent pancreatic graft rejection in type I diabetes patients. In immunocompetent mice receiving transplants of human embryonic stem cell (hESC)-derived pancreatic ectoderm (hESC-PE), a combination of antibodies against the CTLA-4 and CD40L co-stimulatory pathways led to engraftment and differentiation of the transplant into insulin-producing cells and long-term immune tolerance of the graft, whereas no treatment led to transplant rejection. In mice receiving hESC-PE transplants and human peripheral blood monocytes, the antibody combination decreased monocyte-mediated graft rejection compared with no treatment. Next steps could include clinical testing of anti-CTLA-A4 and anti-CD40L antibodies in type I diabetes patients receiving transplants.

Bristol-Myers Squibb Co. and Ono Pharmaceutical Co. Ltd. market the anti-CTLA-4 antibody Yervoy ipilimumab to treat melanoma. At least three other companies have anti-CTLA-4 antibodies in Phase II testing or earlier. At least four companies have anti-CD40L antibodies in Phase I or earlier testing...