A bispecific soluble receptor fusion protein that targets TNF‐α and IL‐21 for synergistic therapy in inflammatory arthritis

Abstract

This study was aimed at investigating the therapeutic effects of BITRAP, a bispecific fusion protein targeting TNF-α and IL-21, on the development of autoimmune arthritis in humans and mice. To verify the effects of BITRAP in human, peripheral blood mononuclear cells were cultured with BITRAP under IL-17-producing T (Th17) cell-polarizing conditions or osteoclast differentiation conditions. BITRAP treatment inhibited the production of IL-17 and vascular endothelial growth factor but increased the production of IL-10 in CD4 + T cells, as well as directly suppressed osteoclastogenesis. Collagen-induced arthritis (CIA) and IL-1R antagonist (IL-1Ra) knockout mice were treated with BITRAP. Following injection in CIA mice, BITRAP rapidly migrated into the inflamed joints and remained there for 72 hours.Application of BITRAP attenuated the severity of autoimmune arthritis in CIA and IL-1Ra knockout mice by reducing the numbers of inflammatory cytokine-expressing cells and Th17 cells and antibody secretion. Finally, BITRAP suppressed STAT3 phosphorylation, as well as production of IL-17 and TNF-α, in murine splenic CD4 + | 249 PARK et Al.

Gaultheria leucocarpa var. yunnanensis for Treating Rheumatoid Arthritis—An Assessment Combining Machine Learning–Guided ADME Properties Prediction, Network Pharmacology, and Pharmacological Assessment

“…The blood samples from all the AIA rats were obtained at day 27 and were anticoagulated with sodium heparin. The levels of IL-1β, TNF-α, IL-6, and IL-2 in the plasma were detected using commercially available rat ELISA kits according to the protocol of the kit, and absorbance was determined at 405 nm ( Park et al, 2020 ).…”

Assessment of the anti‐rheumatoid arthritis activity of Gastrodia elata (tian‐ma) and Radix aconitic lateralis preparata (fu‐zi) via network pharmacology and untargeted metabolomics analyses

“…RA is a common autoimmune disease which might be induced by virus infection, such as Kaposi sarcoma‐associated herpesvirus, 36,37 Epstein‐Barr virus 38,39 and human cytomegalovirus 40 . Our results of targets‐pathways analysis (Figure 8) indicated that the identified compounds from TF couplet were involved in control of inflammation, 41 apoptosis, vascular endothelial function 42 and other RA‐related processes 43‐45 . Signaling pathways such as PI3K/AKT/mammalian target of rapamycin/nuclear factor‐κB is involved in the modulation of autophagy, chondrocytes proliferation and apoptosis of the synovial fibroblasts, all of which are closely linked to RA 46‐50 .…”

The future of drug development for inflammatory bowel disease: the need to ACT (advanced combination treatment)

“…They demonstrated that this BsAb improved inflammation and attenuated bone destruction in arthritic mice. Along these lines BITRAP, a bispecific fusion protein targeting TNFα and IL-21 attenuated disease severity in collagen-induced arthritis and IL-1R antagonist knockout mice via modulation of Th17 cells and osteoclastogenesis 27…”