Fc-Silent Anti-CD154 Domain Antibody Effectively Prevents Nonhuman Primate Renal Allograft Rejection

• DOI: 10.1111/ajt.14197
• Publication Date: 2017-01-18T01:48:08Z
• Authors: S.C. Kim; W. Wakwe; L.B. Higginbotham; D.V. Mathews; C.P. Breeden; A.C. Stephenson; J. Jenkins; E. Strobert; K. Price; L. Price; R. Kuhn; H. Wang; A. Yamniuk; S. Suchard; A.B. Farris; T.C. Pearson; C.P. Larsen; M.L. Ford; A. Suri; S. Nadler; A.B. Adams
• Keywords: CD154; Immunosuppression

The advent of costimulation blockade provides the prospect for targeted therapy with improved graft survival in transplant patients. Perhaps most effective experimental models is use reagents to block CD40/CD154 pathway. Unfortunately, successful clinical translation anti-CD154 has not been achieved. In an attempt develop agent that as previous CD154 blocking antibodies but lacks risk thromboembolism, we evaluated efficacy and safety a novel anti-human domain antibody (dAb, BMS-986004). dAb effectively blocked CD40-CD154 interactions lacked crystallizable fragment (Fc) binding activity resultant platelet activation. nonhuman primate kidney model, was safe efficacious, significantly prolonging allograft without evidence thromboembolism (Median time 103 days). combination conventional immunosuppression synergized control rejection 397 Furthermore, treatment increased frequency CD4+ CD25+ Foxp3+ regulatory T cells. This study demonstrates Fc equally potent agents at renal preclinical model.