BRIEF RESEARCH REPORT article
Front. Vet. Sci.
Sec. Veterinary Pharmacology and Toxicology
Volume 12 - 2025 | doi: 10.3389/fvets.2025.1645414
Tocilizumab Binds to Canine IL-6 Receptor and Elicits In-vitro Inhibitory Biological Response
Provisionally accepted- 1College of Veterinary Medicine, Cornell University, Ithaca, United States
- 2Cornell University Robert Frederick Smith School of Chemical and Biomolecular Engineering, Ithaca, United States
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Tocilizumab (TCZ) is an immunosuppressive drug approved for the treatment of rheumatoid arthritis in humans. Molecularly, it is a humanized monoclonal antibody (mAb) that binds to the interleukin-6 receptor (IL-6R), blocking its inflammatory pathway with the IL-6 protein. No studies have tested its potential use in canine diseases based on species antibody differences. Methods (1)To assess the biological inhibitory effect of TCZ on canine macrophages in vitro (n=3), the median fluorescence intensity of phospho-STAT3 (Y705) was determined using flow cytometry and compared to the inhibitory effect of human macrophages (n=2). (2)To characterize the receptor region of interest in the canine IL-R, homology modeling was performed using MODELLER 10.4 software. (3)To investigate the real-time ligand-binding affinity and kinetic parameters for canine IL-6R with TCZ, surface plasmon resonance (SPR) spectroscopy was used, and results were compared to the human IL-6R interaction with TCZ. Results Our results confirm binding of TCZ with canine IL-6R. In comparison, canine IL-6R binds two orders of magnitude less than human IL-6R in its dissociation constant. Canine cells required a higher concentration of TCZ compared to human cells to produce a similar inhibitory effect. Conclusions and Clinical Significance: The binding of TCZ to canine IL-6R resulting in a biological response is an example of the new possibilities to harness humanized mAb for canine diseases. TCZ may not be a feasible treatment due to the binding affinity and the high concentrations needed. However, future studies should explore potential suitable human mAb for treating canine autoimmune diseases.
Keywords: tocilizumab, canine, IL-6R, Autoimmune, Monoclonal antibody
Received: 11 Jun 2025; Accepted: 22 Aug 2025.
Copyright: © 2025 Merbl, Lopez Baltazar, Byron, Chan, Ehrlich and Yu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yael Merbl, College of Veterinary Medicine, Cornell University, Ithaca, United States
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