Anti-Human IL-6 (Siltuximab) – Fc Muted™

This biosimilar antibody is aseptically packaged and formulated in 0.01 M phosphate buffered saline (150 mM NaCl) PBS pH 7.2 - 7.4 with no carrier protein, potassium, calcium or preservatives added. Due to inherent biochemical properties of antibodies, certain products may be prone to precipitation over time. Precipitation may be removed by aseptic centrifugation and/or filtration.

Liquid

Recombinant biosimilar antibodies are manufactured in an animal free facility using only in vitro protein free cell culture techniques and are purified by a multi-step process including the use of protein A or G to assure extremely low levels of endotoxins, leachable protein A or aggregates.

To protect mouse colonies from infection by pathogens and to assure that experimental preclinical data is not affected by such pathogens, all of Leinco’s recombinant biosimilar antibodies are tested and guaranteed to be negative for all pathogens in the IDEXX IMPACT I Mouse Profile.

Functional grade preclinical antibodies may be stored sterile as received at 2-8°C for up to one month. For longer term storage, aseptically aliquot in working volumes without diluting and store at ≤ -70°C. Avoid Repeated Freeze Thaw Cycles.

Research Use Only

2 – 8° C Wet Ice

This non-therapeutic biosimilar antibody uses the same variable region sequence as the therapeutic antibody Siltuximab. CNTO-328 (Siltuximab) is a neutralizing monoclonal antibody specific against human IL-6.

IL-6 is a pleiotropic 26 kD protein that can act as both a pro-inflammatory cytokine and an anti-inflammatory myokine, a form of cytokine produced in muscle cells that participates in tissue regeneration and repair, maintenance of healthy bodily functioning, and homeostasis within the immune system ¹. IL-6 also plays a part in the endocrine, nervous, and hematopoietic systems, bone metabolism, regulation of blood pressure, and inflammation. Furthermore, IL-6 is an important mediator of fever and of the acute phase response which is the body's rapid attempt to restore homeostasis after tissue injury, infection, neoplastic growth, or immunological disturbance. In its role as an anti-inflammatory myokine, IL-6 precedes the appearance of other cytokines in the circulation, is notably elevated with exercise, and is mediated by both its inhibitory effects on TNF-α and IL-1, and activation of IL-1R⍺ and IL-10. IL-6 signals through a cell-surface type I cytokine receptor complex formed by the binding of IL-6 to IL-6R, which in turn combines with GP130 to transduce extracellular signaling via STAT3 activation. Hence, it is thought that blocking the interaction between IL-6 and GP130 may have therapeutic potential via the inhibition of the IL-6/GP130/STAT3 signaling pathway. Moreover, IL-6 initiates inflammatory and auto-immune processes in many diseases, including diabetes, atherosclerosis, depression, Alzheimer's disease, rheumatoid arthritis, and cancer. For example, multicentric Castleman’s disease is a rare lymphoproliferative disorder caused by dysregulation of IL-6 ². Thus, there is an interest in the therapeutic potential of anti-IL-6 mAbs.

CNTO-328 (Siltuximab) is a chimeric monoclonal antibody that was developed for the treatment of IL-6 related disorders ^2,3,4,5. Siltuximab is associated with sustained reductions in IL-6 levels along with various other cytokines and markers ². In vitro studies in ovarian cancer cells show that siltuximab inhibits IL-6 induced STAT3 activation, nuclear translocation, and downstream gene expression ⁶. Siltuximab also induces apoptosis ^2,7 and reduces C-reactive protein levels ².

Siltuximab has been approved for the treatment of multicentric Castleman’s disease in HIV-negative patients ¹. Siltuximab does not bind to virally produced IL-6 (vIL-6).

IL-6 is a pleiotropic cytokine produced by B lymphocytes, T lymphocytes, macrophages, microglia, fibroblasts, keratinocytes, mesangial cells, vascular endothelial cells, mast cells, and dendritic cells. Additionally, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smooth muscle cells in the tunica media of many blood vessels produce IL-6 as a pro-inflammatory cytokine. IL-6 is also released into circulation in response to various stimuli including PAMPs (pathogen-associated molecular patterns) and cortisol, a hormone produced by the human body under psychologically stressful conditions.

IL6R

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