Olokizumab Overview

Introduction of Olokizumab

Olokizumab (CDP6038), a humanized monoclonal antibody (mAb) specific for the interleukin-6 (IL-6) cytokine, is currently in development for the treatment of rheumatoid arthritis (RA). It targets the IL-6 cytokine rather than the receptor, and selectively blocks the final assembly of the signalling complex. In Phase I (healthy volunteers) and IIa (patients with RA on MTX) clinical trials, olokizumab was well tolerated after intravenous and subcutaneous delivery with a median plasma half-life of approximately 31 days, 76% bioavailability and no apparent antidrug antibody-mediated clearance. Olokizumab also markedly reduced free IL-6 levels and suppressed C-reactive protein (CRP) up to 12 weeks after single-dose subcutaneous administration in patients with RA.

Mechanism of Action of Olokizumab

Interlukin-6 (IL-6) is a multifunctional cytokine with a central role in inflammation, infection responses, regulation of metabolic, regenerative, and neural processes. It has broad effect on cells of the immune system and is produced by T and B lymphocytes, fibroblasts, monocytes, keratinocytes, mesangial and endothelial cells, and several tumor cells. Normal physiological concentrations of IL-6 in human serum are relatively low, but rapidly elevated during infection, autoimmunity, and inflammation. IL-6 deficiency leads to impaired innate and adaptive immunity to viral, parasitic, and bacterial infection. In contrast, excessive production of IL-6 may leads to chronic autoimmune as well as inflammatory diseases such as psoriasis, rheumatoid arthritis, systemic lupus erythematosus, systemic juvenile idiopathic arthritis, Crohn’s disease, and tumorigenesis. Therefore, IL-6 has context-dependent pro- and anti-inflammatory properties and considered as a prominent target for clinical interventions. IL-6 has three distinct conserved epitopes: Site I, Site II, and Site III. IL-6, first form a complex with nonsignaling receptor, IL-6R (also known as gp80, CD126), through Site I and then form composite epitope known as Site II which interacts with cytokine-binding homology region of glycoprotein 130 (gp130) to constitute IL-6R:IL-6:gp130 trimer. Subsequent interaction of IL-6 Site III with gp130 immunoglobulin-like activation domain of two trimers form competent biologically active hexameric (ternary) signaling complex and activate Janus kinase (JAK) / signal transducer and activator of transcription-3 (STAT-3) pathway leading to inflammation. Olokizumab targets IL-6 itself but not IL-6R to restrict the cytokine to form hexameric signaling complex and nullify inflammation due to IL-6 over expression.

Fig.1 Mechanism of action of olokizumab

Clinical Projects of Olokizumab*

What We Provide

Therapeutic Antibody

Olokizumab

We provide high-quality Olokizumab for use in WB, FC, IP, ELISA, Neut, FuncS, IF and most other immunological methods. For lab research use only, not for diagnostic, therapeutic or any in vivo human use.

* The table was excerpted from the following website
https://clinicaltrials.gov/ct2/results?cond=&term=Olokizumab

For research use only. Not intended for any clinical use.