Characterization of anti-canine cytokine monoclonal antibodies specific for IFN-gamma: effect of anti-IFN-gamma on renal transplant rejection

• Published in: Tissue antigens Vol. 43; no. 3; p. 163
• Main Authors: Fuller, L, Carreno, M, Esquenazi, V, Zucker, K, Zheng, S, Roth, D, Burke, G, Nery, J, Asthana, D, Olson, L
• Format: Journal Article
• Language: English
• Published: England 01.03.1994
• Subjects: Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - therapeutic use; Antibody Affinity; Dogs - immunology; Enzyme-Linked Immunosorbent Assay; Graft Rejection - prevention & control; Humans; Immunoglobulin G - immunology; Interferon-gamma - antagonists & inhibitors; Interferon-gamma - immunology; Kidney Transplantation - immunology; Mice; Mice, Inbred BALB C; Recombinant Proteins
• ISSN: 0001-2815
• DOI: 10.1111/j.1399-0039.1994.tb02317.x

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.