Fc-disabled anti-mouse CD40l antibodies retain efficacy in promoting transplantation tolerance

S. R. Daley, S. P. Cobbold, H. Waldmann

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21 Citations (Scopus)


CD40L antibodies have proven to be powerful immunosuppressive agents in nonhuman primates but unfortunately perturb blood coagulation. Neither the therapeutic nor the prothrombotic mechanism of anti-CD40L is defined sufficiently to determine whether these effects can be uncoupled. Recent evidence suggests that the Fc region of anti-CD40L antibodies interacting with Fc receptors plays an important role in stabilizing platelet aggregates. An Fc-disabled, aglycosylated anti-CD40L heavy chain variant was therefore created to determine whether it might still be useful in promoting transplantation tolerance. In a number of mouse models an engineered aglycosyl anti-CD40L recapitulated the effects of the intact anti-CD40L antibody in tolerance protocols involving transplantation of allogeneic bone marrow and skin. In contrast, another anti-CD40L variant with a conventional rat γ2b heavy chain was less effective in ensuring long-term skin graft survival, possibly associated with its faster clearance from the circulation. These results show that short pulses of anti-CD40L antibody therapy may still be useful in tolerance protocols even when the Fc region is disabled.

Original languageEnglish
Pages (from-to)2265-2271
Number of pages7
JournalAmerican Journal of Transplantation
Issue number11
Publication statusPublished - 1 Nov 2008
Externally publishedYes


  • Allograft tolerance
  • Anti-CD154 monoclonal antibody
  • Antibodies
  • Transplant immunology
  • Transplant tolerance
  • Venous thromboembolism

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