Human IL-6R Antibody Family

Tocilizumab biosimilar isotypes: IgG1, IgG1NQ, and IgA2

Human monoclonal antibody (mAb) isotypes against human IL-6R

InvivoGen provides a family of anti-hIL-6R-derived monoclonal antibodies (mAbs) in multiple human isotypes.

They feature:

  • the variable region of tocilizumab targeting the human interleukin 6 receptor (hIL-6R)
  • a strong>constant region that mediates different effector functions depending on the isotype.

The effector functions of the human isotypes in this family include antibody‑dependent cell-mediated cytotoxicity/phagocytosis (ADCC/ADCP) and complement-dependent cytotoxicity (CDC). You may choose between:

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— IgG1 for high effector functions
     (Anti-hIL6R-hIgG1 is the biosimilar of the clinical antibody tocilizumab ),

— IgG1NQ for no effector functions
     (engineered N-glycosylation mutated constant region).

— IgA2 for low effector functions
      (low ADCC/ADCP, and no CDC)

InvivoGen's mAbs have been generated by recombinant DNA technology, produced in Chinese hamster ovary (CHO) cells, and purified by affinity chromatography.

Key features of the Anti-hIL-6R isotype family

  • Clinically-relevant variable region targeting human IL-6 receptor (varlilumab)
  • Choice of different constant regions for high/low effector functions
  • Functionally validated by flow cytometry and ELISA
  • The absence of bacterial contamination has been confirmed

IL-6R background

Tocilizumab (TCZ) is a recombinant, humanized monoclonal antibody (mAb) directed against both soluble and membrane-bound human IL-6R. TCZ exhibits anti-inflammatory activity by inhibiting the binding of the pro-inflammatory cytokine, IL-6 to its receptor [1]. IL-6 exerts its biological effects through IL-6R, and the transmembrane protein gp130. Despite only a few cells expressing IL-6R on their surface, many cells respond to IL-6 due to the existence of soluble IL-6R [2]. TCZ can block both modes of signaling [1]. TCZ has been approved for the treatment of inflammatory diseases and conditions such as rheumatoid arthritis (RA) and cytokine release syndrome (CRS), a side effect of CAR-T therapy. Furthermore, it is under investigation for the treatment of the late-stage hyperinflammation observed in severe COVID‑19 patients [3].

 

References

1. Sheppard, M. et al. 2017. Tocilizumab (Actemra). Hum Vaccin Immunother 13, 1972- 1988.
2. Rose-John, S. 2012. IL-6 trans-signaling via the soluble IL-6 receptor: importance for the pro-inflammatory activities of IL-6. Int J Biol Sci 8, 1237-1247.
3. Zhang, S. et al. 2020. Rational Use of Tocilizumab in the Treatment of Novel Coronavirus Pneumonia. Clin Drug Investig.