Anti-Human IL-6R (Tocilizumab) (I1240-GRP)

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 .