IL-10   Click here for help

GtoPdb Ligand ID: 4975

Synonyms: interleukin-10
Immunopharmacology Ligand
Comment: Biologically active IL-10 is a homodimer. It is an anti-inflammatory cytokine.
Species: Human
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Immunopharmacology Comments
Interleukin-10 (IL-10) is a type II cytokine and the originating member of a family of structurally related cytokines that includes IL-19, IL-20, IL-22, IL-24, IL-26, IL-28, and IL-29. All family members activate JAK/STAT signalling pathways. Variety in biological activities is determined by the cells producing the cytokine, the cells responding to them, and the local immune environment exposed to them.
IL-10 is an anti-inflammatory cytokine principally produced by T-helper type 2 (Th2) cells, subsets of regulatory T cells designated Tr1, Th1, and Th17 cells [5]. CD8+ T cells, monocytes, stimulated macrophages, subsets of dendritic cells (DCs), B cells [1] and granulocytes (e.g. eosinophils and mast cells [6]) also produce IL-10 to some extent. Some non-immune cells such as keratinocytes, epithelial cells, and tumor cells are sources of IL-10.

An immunocytokine that fuses IL-10 to an antibody to the extra-domain A of fibronectin called Dekavil (F8-IL10) was in clinical development as an anti-rheumatoid arthritis (RA) therapy [7]. The rationale of this pharmacodelivery approach is that the monoclonal part of the agent will more effectively deliver the IL-10 to sites of disease, to increase its concentration at target tissues, but spare normal tissues. Dekavil was advanced to a Phase 2 safety and efficacy clinical trial in RA patients who were receiving methotrexate therapy (NCT02270632). However, Pfizer's pipeline webpage indicates that the dekavil program has since been discontinued.

A pegylated version of hIL-10 (AM0010 ; INN pegilodecakin) is being investigated for immuno-onclogy potential in patients with advanced solid tumours [4]. The most advanced trial is NCT02923921, which is a Phase 3 study that is evaluating AM0010 plus FOLFOX chemotherapy as second-line therapy for patients with metastatic pancreatic cancer. In this study the combination treatment is being directly compared to FOLFOX alone. AM0010 achieves its anti-tumour effect through activation of CD8+ T cell immunity which overcomes the cancer-induced state of intratumoural tumour-reactive T cell exhaustion [3].
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