Preclinical development of GR1501, a human monoclonal antibody that neutralizes interleukin-17A

Abstract

Interleukin-17A (IL-17A) is a soluble pro-inflammatory cytokine, which is mainly secreted by Th17 cells. In humans, IL-17A mRNA and protein levels are increased in several autoimmune diseases, including psoriasis and rheumatoid arthritis. This study describes the preclinical in vitro and in vivo characterization of GR1501, a human IL-17A-neutralizing IgG4 monoclonal antibody. GR1501 binds human, rhesus and cynomolgus IL-17A with high affinity but does not bind to mouse IL-17A or other IL-17 family members. GR1501 effectively blocks the interaction between IL-17A and its receptor IL-17RA, thereby inhibiting IL-17A-induced CXCL1 and IL-6 release in cells and mice. In mouse air pouch model, GR1501 effectively inhibits IL-17A induced leukocytes infiltration into the air pouch. GR1501 also reduces joint swelling and inflammation in mouse arthritis model. These data suggest that GR1501 is a potent and selective IL-17A-neutralizing monoclonal antibody and will support the clinical investigation of this monoclonal antibody in psoriasis and rheumatoid arthritis.

Keywords: Arthritis; GR1501; IL-17A monoclonal antibody; Preclinical development.