IDEC-131 (anti-CD154), sirolimus and donor-specific transfusion facilitate operational tolerance in non-human primates
Edwin H Preston, He Xu, Kiran K Dhanireddy, Jonathan P Pearl, Frank V Leopardi, Matthew F Starost, Douglas A Hale, Allan D Kirk, Edwin H Preston, He Xu, Kiran K Dhanireddy, Jonathan P Pearl, Frank V Leopardi, Matthew F Starost, Douglas A Hale, Allan D Kirk
Abstract
CD154-specific antibody therapy prevents allograft rejection in many experimental transplant models. However, initial clinical transplant trials with anti-CD154 have been disappointing suggesting the need for as of yet undetermined adjuvant therapy. In rodents, donor antigen (e.g., a donor blood transfusion), or mTOR inhibition (e.g., sirolimus), enhances anti-CD154's efficacy. We performed renal transplants in major histocompatibility complex-(MHC) mismatched rhesus monkeys and treated recipients with combinations of the CD154-specific antibody IDEC-131, and/or sirolimus, and/or a pre-transplant donor-specific transfusion (DST). Therapy was withdrawn after 3 months. Triple therapy prevented rejection during therapy in all animals and led to operational tolerance in three of five animals including donor-specific skin graft acceptance in the two animals tested. IDEC-131, sirolimus and DST are highly effective in preventing renal allograft rejection in primates. This apparently clinically applicable regimen is promising for human renal transplant trials.
Source: PubMed