GM-CSF: The new favorite of rheumatism immunity, the new crown CRS will be approved soon

On May 28, 2021, the company Humanigen ((Nasdaq:HGEN), which focuses on the development of cytokine storm (CRS) drugs, submitted an emergency use authorization application for the GM-CSF antibody Lenzilumab to the FDA based on good phase 3 clinical data.
Use Authorization, EUA), is expected to become the first GM-CSF monoclonal antibody approved for clinical use for the new crown CRS indication
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GM-CSF and the new crown CRS (Document 1) GM-CSF physiological function GM-CSF was the first as a kind of Hematopoietic growth factor was found to stimulate bone marrow precursor cells to form granulocytes and macrophages, so it was named Granulocyte macrophage-colony stimulating factor (Granulocyte macrophage-colony stimulating factor, GM-CSF) (Reference 2)
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GM-CSF has a wide range of physiological functions, mainly promoting the production, differentiation, activation, and survival of granulocytes and macrophages
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In addition, it is also a key homeostasis factor in the alveoli.
At low levels, it is used for alveolar macrophages.
Development and long-term maintenance.
In the absence of GM-CSF, pulmonary alveolar proteinopathy (PAP) occurs, and the function of pulmonary macrophages is defective, which increases the risk of lung infection
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CSF family and its function (Reference 3) GM-CSF and itself Immunological diseases GM-CSF is secreted by epithelial cells and white blood cells (such as specific Th cell subsets), and the GM-CSF receptor is expressed in myeloid cells
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The role of GM-CSF in the immune response is mainly two types: 1.
Polarize mature myeloid cells into a pro-inflammatory phenotype (paracrine/autocrine function); 2.
Control "emergency bone marrow production" and differentiate progenitor cells For myeloid cells, expand and mobilize to the inflammation site (endocrine function)
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GM-CSF is widely involved in various inflammatory diseases, especially autoimmune diseases such as rheumatoid arthritis
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GM-CSF promotes the transport of monocytes and macrophages to inflammatory tissues, such as the synovial joints of rheumatoid arthritis (RA), and promotes their activation, differentiation, survival and proliferation at the inflammatory site
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The activated M1 macrophages produce cytokines, including GM-CSF and other pro-inflammatory cytokines (such as TNF, IL-6, IL-1, and chemokines)
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These mediators promote the recruitment of inflammatory cells and the activation of resident fibroblast-like synoviocytes (FLSs)
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The production of local GM-CSF leads to the activation of the vascular system and bone marrow, and promotes the differentiation of effector T cells at the site of inflammation and draining lymph nodes
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GM-CSF promotes the differentiation of infiltrating monocytes into M1 macrophages and monocyte-derived dendritic cells (MoDCs) to regulate the phenotype of antigen-presenting cells in inflammatory tissues
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IL-23 is produced by macrophages and MoDCs, combined with other cytokines (such as IL-6 and IL-1), to regulate the differentiation of T cells into Th17
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Th17 is an important pathological cell subtype of rheumatic diseases
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GM-CSF is involved in inflammatory diseases such as rheumatoid arthritis (Document 4) Targeting GM-CSF antibody drugs Because GM-CSF is widely involved in inflammatory diseases and the cytokine storm induced by the new crown, it includes Humanigen, GlaxoSmithKline, Many products at home and abroad, including Tianjing, are under research, and the main indications are rheumatoid arthritis and COVID-19
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Some of the products under research are shown in the following table: The editor concludes that GM-CSF is an important cytokine that participates in the differentiation, development, and activation of granulocytes and macrophages, and maintains the physiological functions of alveoli
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GM-CSF is also widely involved in inflammation, induces myeloid cells to differentiate into an inflammatory phenotype, recruits and promotes immune cells to release cytokines and chemokines, and further aggravates inflammation, thus becoming an important target for rheumatoid arthritis and neocorona cytokine storm Point
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Many international and domestic companies have GM-CSF in their pipelines.
Among them, GlaxoSmithKline has the fastest progress in rheumatoid arthritis, and multiple phase III clinical trials are underway; COVID-19Humanigen has submitted EUA
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References 1.
Bonaventura A, Vecchié A, Wang TS, Lee E, Cremer PC, Carey B, Rajendram P, Hudock KM, Korbee L, Van Tassell BW, Dagna L and Abbate A (2020) Targeting GM-CSF in COVID- 19 Pneumonia: Rationale and Strategies.
Front.
Immunol.
11:1625.
doi: 10.
3389/fimmu.
2020.
016252.
Burgess AW, Metcalf D.
The nature and action of granulocyte-macrophage colony stimulating factors.
Blood.
(1980) 56:947-- 58.
3.
Becher, B.
, Tugues, S.
& Greter, M.
GM-CSF: from growth factor to central mediator of tissue inflammation.
Immunity 45, 963–973 (2016).
4.
Ian P.
Wicks and Andrew W.
Roberts, Targeting GM‑CSF in inflammatory diseases, NATURE REVIEWS | RHEUMATOLOGY, doi:10.
1038/nrrheum.
2015.
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