Abstract

Tolerance to organ allografts in rodents and pigs can be easily achieved. However, tolerance induction in a large primate model has been more elusive. In this study, we have used an anti-CD4, murine monoclonal antibody as a carrier for the cytotoxic drug idarubicin (IDA) to delete or inactivate alloreactive T-cells responding to a renal allograft in a baboon transplant model. Fourteen Chacma baboons weighing between 15-25 kg received heterotopic renal allografts. Recipient and donor pairs were selected on the basis of ABO compatibility. Seven animals were given no immunosuppression and served as the control group. The remaining 7 animals received anti-CD4 IDA. The first 2 animals in this group received 2 mg IVI intraoperatively and three doses at 48-h intervals thereafter. The last 5 animals received a larger dose of 1 mg/kg, starting 24 h preoperatively and again on postoperative days 2 and 5. The untreated animals promptly rejected their allografts with a mean survival of 10 days. The survival of the 2 animals treated with 2 mg anti-CD4 IDA was 7 days each. However, the animals treated with 1 mg/kg anti-CD4 IDA survived 7, 18, 20, 40 and > 40 days. Peritransplant administration of anti-CD4 IDA prolonged renal allograft survival in a large primate model. This unique immunoconjugate has the potential of tolerance induction.