Characterization of anti-canine cytokine monoclonal antibodies specific for IFN-gamma: effect of anti-IFN-gamma on renal transplant rejection.
Two murine monoclonal antibodies specific for IFN-gamma, ADI-1, and ADI-23 (both IgG1 kappa), were generated in BALB/c mice. The ADI-1 exhibited a higher avidity for canine rIFN-gamma than for nIFN-gamma and human rIFN-gamma. In contrast, the ADI-23 showed equal avidity for the three IFN-gamma preparations. The anti-canine IFN-gamma mAb did not bind to mouse and rat rIFN-gamma. The ADI-1, and ADI-23 mAb were also tested for binding to human rTFN-alpha and, contrary to our expectations, it was found that ADI-23 showed significant binding to human rTFN-alpha and rIFN-gamma, in contrast to ADI-1. Both anti-canine IFN-gamma mAb stained 48-h PHA-induced dog lymphoblasts. A two-site mAb ELISA was developed, which was linear in the range of 7-500 ng of canine rIFN-gamma, which indicated that the two mAb detected non-overlapping epitopes on the canine rIFN-gamma molecule. We studied the effect of ADI-1 on the prolongation of canine renal allografts. Recipients of kidney allografts, that were treated with ADI-1 by continuous arterial infusion, were prolonged to 22 and 25 days, compared to 9 and 13 days for animals given the IgG1 isotype control.
Fuller
L
L
Department of Surgery, University of Miami School of Medicine, Florida.
Carreno
M
M
Esquenazi
V
V
Zucker
K
K
Zheng
S
S
Roth
D
D
Burke
G
G
Nery
J
J
Asthana
D
D
Olson
L
L
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D000915:Antibody Affinity; D004285:Dogs / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D007371:Interferon-gamma