Anti-Human IL-6R (Tocilizumab)

Humanized antibody derived from mouse clone PM-1

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 biosimilar 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 -80°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 Tocilizumab. Tocilizumab activity is directed against IL-6R.

IL-6 is a pleiotropic cytokine that promotes B cell and T cell proliferation and differentiation and is also involved in the inflammatory response ¹ . In the ‘classic’ signaling paradigm, IL-6 binds to its membrane bound receptor IL-6R to initiate intracellular signaling pathways ². Alternatively, in ‘trans-signaling’, IL-6 binds to a soluble form of IL-6R. In both events, a complex set of interactions with membrane-bound or soluble β-receptor glycoprotein 130 (gp130) modulates the downstream signaling pathways. Additionally, IL-6 plays an inflammatory role in autoimmune diseases ³ and high IL-6 levels are a feature of cytokine storm and cytokine release syndrome during COVID-19 infection¹ . IL-6 signaling can be inhibited by antibodies directed against IL-6R ³.

Tocilizumab is the first IL-6R inhibitor³ . It competitively inhibits the binding of IL-6 to both soluble and membrane bound IL-6R ^{3, 4}, and thereby prevents IL-6 signal transduction to inflammatory mediators that summon B and T cells ³.

Tocilizumab is a chimeric murine-human antibody engineered by CDR grafting of the antigen binding regions of murine antihuman IL-6R antibody PM-1 to the human IgG1 framework ^{3, 5}. Tocilizumab binds to the IL-6 binding site and neutralizes IL-6 activity ^{5, 6, 7}. Tocilizumab has been studied for the treatment of many autoimmune diseases including rheumatoid arthritis, systemic juvenile idiopathic arthritis, Castleman disease, and Crohn’s disease ⁷ as well as for the treatment of severe COVID-19 ¹ .

IL-6R is expressed on hepatocytes and certain subpopulations of leukocytes.

IL-6 & ciliary neurotrophic factor

1 Cortegiani A, Ippolito M, Greco M, et al. Pulmonology. 27(1):52-66. 2021.
2 Wolf J, Rose-John S, Garbers C. Cytokine. 70(1):11-20. 2014.
3 Sebba A. Am J Health Syst Pharm. 65(15):1413-1418. 2008.
4 Mihara M, Kasutani K, Okazaki M, et al. Int Immunopharmacol. 5(12):1731-1740. 2005.
5 Sato K, Tsuchiya M, Saldanha J, et al. Cancer Res. 53(4):851-856. 1993.
6 Tsunenari T, Koishihara Y, Nakamura A, et al. Blood. 90(6):2437-2444. 1997.
7 Yao X, Huang J, Zhong H, et al. Pharmacol Ther. 141(2):125-139. 2014.