IL-20 (Interleukin-20) is a member of IL-10 family, which includes IL-10, IL-19, IL-22, IL-24, IL-26, IL-28, and IL-29. Besides, IL-20 is mainly produced by myeloid cells such as monocytes, granulocytes, and dendritic cells but can also be produced by keratinocytes and fibroblasts. Importantly, IL-20 shows effects in several inflammatory diseases, such as rheumatoid arthritis, atherosclerosis, cancer, and liver fibrosis via regulating cytokines and chemokines. Particularly, IL-20 acts on renal cells and contributes to inflammation, fibrosis, and apoptosis through its receptors IL-20R1, IL-20R2, and IL-22R1.
IL-20 and its receptors induce apoptosis and necrosis in tubular epithelial cells by activating caspase-9. Specifically, IL-20 upregulates TGF-β1 expression in proximal tubule epithelial cells and promotes IL-1β expression under hypoxic conditions. Moreover, In vivo experiments show that blocking IL-20 with specific antibodies can reduce inflammation and improve disease progression. Here, we will introduce an IL-20 antibody, Fletikumab.
Fletikumab (NNC0109-0012) is a monoclonal antibody (mAb) targeting IL-20.
Fletikumab, a recombinant human anti-IL-20 mAb, blocks IL-20 binding IL-20 receptor and acts with the potential function of inflammation inhibition. Also, Fletikumab is a human antibody (IgG4) that shows high affinity with a Kd value of 37 pM. Meanwhile, It shows a very high potency in blocking IL-20 mediated activity on IL-20RA/IL-20RB and IL-22RA1/IL20R2 expressing cells with an IC50 value of 0.27 nM. Moreover, this compound shows a serum half-life of ~3 weeks in RA (Rheumatoid Arthritis) patients. Additionally, Fletikumab has been tested in two clinical trials, psoriasis and RA. Particular (0.05 to 3.0 mg/kg) shows tolerable and non-toxic in patients with psoriasis. Moreover, Fletikumab significantly reduced tender joint counts and swollen joint counts in seropositive RA patients.
In a word, Fletikumab is a monoclonal antibody against interleukin-20 (IL20) for the treatment of rheumatoid arthritis.