Targeting the major pro-inflammatory interleukin-6-type cytokine receptor gp130 by antagonistic single domain antibodies.

Introduction: Although Interleukin (IL)-6-type cytokine signaling is critical for maintaining the body's homeostasis, aberrant signaling has been observed in numerous diseases including autoimmunity and cancer. Currently, all approved biologics that inhibit IL-6-type cytokines specifically target the key pro-inflammatory mediator IL-6 or its receptor (IL6R). Historically, direct inhibition of glycoprotein 130 (gp130)-the shared transmembrane receptor for IL-6-type cytokines-was avoided due to concerns that broad suppression might cause more harm than benefit.