Anti-CD45RB monoclonal antibody prolongs renal allograft survival in cynomolgus monkeys.
Previously, an anti-CD45RB monoclonal antibody (mAb) has been shown to induce murine allograft tolerance. The present study was performed to assess the ability of an anti-human CD45RB mAb to prevent rejection in a monkey MHC-mismatched kidney transplant model. The recipients were allocated into the following treatment groups: (1) isotype control IgG; (2) mouse anti-human CD45RB IgG1 (6G3); (3) human-mouse chimeric anti-CD45RB-IgG1 (C6G3-IgG1); (4) human-mouse chimeric anti-CD45RB-IgG2 (C6G3-IgG2); (5) tacrolimus at a subtherapeutic dose and (6) tacrolimus and C6G3-IgG1 in combination. Monotherapy with anti-CD45RB mAb significantly prolonged renal allograft survival to a median survival of 21 days. Adding a subtherapeutic dose of tacrolimus improved the efficacy of the anti-CD45RB mAb, achieving a median survival of 85 days, whereas a subtherapeutic dose of tacrolimus alone only moderately prolonged survival to 27 days. Treatment with anti-CD45RB mAb resulted in an alteration of the CD45RB(hi) : CD45RB(lo) cell ratio in the peripheral blood. We have, for the first time, demonstrated that an anti-human CD45RB mAb (6G3) can prolong graft survival. Induction with an anti-CD45RB mAb improves the efficacy of tacrolimus in the prevention of rejection. These encouraging results indicate that an anti-CD45RB mAb may be valuable in future clinical transplantation.
Chen
G
G
Department of Surgery, The University of Western Ontario, London, Ontario, N6A 5C1, Canada.
Luke
P P W
PP
Yang
H
H
Visser
L
L
Sun
H
H
Garcia
B
B
Qian
H
H
Xiang
Y
Y
Huang
X
X
Liu
W
W
Senaldi
G
G
Schneider
A
A
Poppema
S
S
Wang
H
H
Jevnikar
A M
AM
Zhong
R
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D016030:Kidney Transplantation / Q000379:methods*; D017493:Leukocyte Common Antigens / Q000276:immunology*; D008252:Macaca fascicularis; D016559:Tacrolimus / Q000008:administration & dosage; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D017493:Leukocyte Common Antigens; D016559:Tacrolimus