Abstract
Interleukin-6 (IL-6) is a critical regulator of the immune system and has been widely implicated in autoimmune disease. Here, we describe the discovery and characterization of olokizumab, a humanized antibody to IL-6. Data from structural biology, cell biology and primate pharmacology demonstrate the therapeutic potential of targeting IL-6 at "Site 3", blocking the interaction with the signaling co-receptor gp130.
Keywords:
IL-6; antibody; gp130; interleukin 6; neutralization; olokizumab; site 3; structure.
MeSH terms
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Amino Acid Sequence
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Animals
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Antibodies, Monoclonal, Humanized / chemistry
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Antibodies, Monoclonal, Humanized / genetics
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Antibodies, Monoclonal, Humanized / immunology*
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Antibodies, Neutralizing / chemistry
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Antibodies, Neutralizing / genetics
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Antibodies, Neutralizing / immunology*
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Antigen-Antibody Complex / chemistry
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Arthritis, Experimental / immunology
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Arthritis, Experimental / therapy
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Binding Sites
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Crystallography, X-Ray
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Cytokine Receptor gp130 / antagonists & inhibitors*
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Cytokine Receptor gp130 / chemistry
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Cytokine Receptor gp130 / immunology*
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Female
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Humans
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Hybridomas / immunology
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Immunoglobulin Fab Fragments / chemistry
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Immunoglobulin Fab Fragments / genetics
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Immunoglobulin Fab Fragments / immunology
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Interleukin-6 / antagonists & inhibitors*
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Interleukin-6 / chemistry
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Interleukin-6 / immunology*
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Macaca fascicularis
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Models, Molecular
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Molecular Sequence Data
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Rats
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Sequence Homology, Amino Acid
Substances
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Antibodies, Monoclonal, Humanized
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Antibodies, Neutralizing
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Antigen-Antibody Complex
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IL6 protein, human
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Immunoglobulin Fab Fragments
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Interleukin-6
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Cytokine Receptor gp130
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olokizumab