Effects of combined treatment with CD25- and CD154-specific monoclonal antibodies in non-human primate allotransplantation.
The CD154-specific monoclonal antibody (Mab) hu5c8 greatly prolongs allograft survival in primates. The CD25-specific Mab daclizumab has not, to date, been paired with hu5c8. We evaluated the effects of hu5c8 in vitro, alone and in combination with daclizumab on rhesus-mixed lymphocyte reactions (MLRs). We then evaluated therapy with hu5c8 and daclizumab in four monkey renal allograft recipients compared with monkeys untreated or contemporaneously treated with hu5c8 alone. Lymphocyte proliferation in MLR was reduced by both daclizumab and hu5c8, and their combined effects were additive. Rejection-free allograft survival in monkeys treated with both hu5c8 and daclizumab (74-479 days) was not significantly better than animals treated with hu5c8 alone (257-587 days), and one combined therapy animal rejected while still on hu5c8 therapy, a condition not typically seen with hu5c8 monotherapy. Although daclizumab and hu5c8 are additively effective in MLR, they do not appear to be synergistic in vivo in rhesus monkeys.
Xu
He
H
Transplantation and Autoimmunity Branch, National Institute of Diabetes, Digestive and Kidney Disease, National Institutes of Health, Bethesda, MD 20892, USA.
Elster
Eric A
EA
Blair
Patrick J
PJ
Burkly
Linda C
LC
Tadaki
Douglas K
DK
Harlan
David M
DM
Kirk
Allan D
AD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D023201:CD40 Ligand / Q000737:chemistry*; D002455:Cell Division; D000077561:Daclizumab; D006085:Graft Survival; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016030:Kidney Transplantation / Q000379:methods*; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008253:Macaca mulatta; D015375:Receptors, Interleukin-2 / Q000737:chemistry*; D014184:Transplantation, Homologous / Q000379:methods*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; C442103:hu5C8 antibody; D023201:CD40 Ligand; D000077561:Daclizumab