Open AccessProlonged survival of baboon renal allografts using idarubicin‐conjugated anti‐CD4 monoclonal antibodies
Author(s) -
Botha J.F.,
Tandon V.,
Linley W.,
Mall A.,
Davison G.,
Shephard E.,
McKenzie I.F.C.,
Kahn D.
Publication year - 2000
Publication title -
transplant international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.998
H-Index - 82
eISSN - 1432-2277
pISSN - 0934-0874
DOI - 10.1111/j.1432-2277.2000.tb02089.x
Subject(s) - medicine , baboon , monoclonal antibody , immunosuppression , transplantation , kidney , immunoconjugate , antibody , urology , surgery , immunology
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 pre‐operatively 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.