A novel monoclonal antibody to CD40 prolongs islet allograft survival

M. Lowe, I. R. Badell, P. Thompson, B. Martin, F. Leopardi, E. Strobert, A. A. Price, H. S. Abdulkerim, R. Wang, N. N. Iwakoshi, A. B. Adams, A. D. Kirk, C. P. Larsen*, K. A. Reimann

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

71 Scopus citations


The importance of CD40/CD154 costimulatory pathway blockade in immunosuppression strategies is well-documented. Efforts are currently focused on monoclonal antibodies specific for CD40 because of thromboembolic complications associated with monoclonal antibodies directed towards CD154. Here we present the rational development and characterization of a novel antagonistic monoclonal antibody to CD40. Rhesus macaques were treated with the recombinant anti-CD40 mAb, 2C10, or vehicle before immunization with keyhole limpet hemocyanin (KLH). Treatment with 2C10 successfully inhibited T cell-dependent antibody responses to KLH without significant peripheral B cell depletion. Subsequently, MHC-mismatched macaques underwent intraportal allogeneic islet transplantation and received basiliximab and sirolimus with or without 2C10. Islet graft survival was significantly prolonged in recipients receiving 2C10 (graft survival time 304, 296, 265, 163 days) compared to recipients receiving basiliximab and sirolimus alone (graft survival time 8, 8, 10 days). The survival advantage conferred by treatment with 2C10 provides further evidence for the importance of blockade of the CD40/CD154 pathway in preventing alloimmune responses. 2C10 is a particularly attractive candidate for translation given its favorable clinical profile. 2C10, a novel antagonistic monoclonal antibody to CD40, inhibits antigen-specific T cell-dependent antibody responses and significantly prolongs islet allograft survival in nonhuman primates.

Original languageEnglish
Pages (from-to)2079-2087
Number of pages9
JournalAmerican Journal of Transplantation
Issue number8
StatePublished - Aug 2012
Externally publishedYes


  • Co-stimulation blockade
  • immunosuppressive therapy
  • islet transplantation
  • type 1 diabetes mellitus


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