Prolonged survival of baboon renal allografts using idarubicin-conjugated anti-CD4 monoclonal antibodies.
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.
Botha
J F
JF
Department of Surgery, University of Cape Town, Medical School, Observatory, South Africa.
Tandon
V
V
Linley
W
W
Mall
A
A
Davison
G
G
Shephard
E
E
McKenzie
I F
IF
Kahn
D
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015704:CD4 Antigens / Q000276:immunology; D005260:Female; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D000922:Immunotoxins / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D010215:Papio; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D007166:Immunosuppressive Agents; D000922:Immunotoxins