Granulocyte-macrophage colony-stimulating factor

Granulocyte-macrophage colony-stimulating factor

Clinical data
ATC code	L03AA09 (WHO)
Identifiers
IUPAC name Human granulocyte macrophage colony stimulating factor
CAS Number	83869-56-1 Y
DrugBank	DB00020 N
ChemSpider	none
Chemical and physical data
Formula	C639H1006N168O196S8
Molar mass	14434.54 g·mol−1
NY (what is this?)  (verify)

Granulocyte-macrophage colony-stimulating factor (GM-CSF), also known as colony-stimulating factor 2 (CSF2), is a

Unlike granulocyte colony-stimulating factor, which specifically promotes neutrophil proliferation and maturation, GM-CSF affects more cell types, especially macrophages and eosinophils.^[5]

Function

GM-CSF is a

GM-CSF also has some effects on mature cells of the immune system. These include, for example, enhancing neutrophil migration and causing an alteration of the receptors expressed on the cells surface.[7]

GM-CSF signals via signal transducer and activator of transcription, STAT5.^[8] In macrophages, it has also been shown to signal via STAT3. The cytokine activates macrophages to inhibit fungal survival. It induces deprivation in intracellular free zinc and increases production of reactive oxygen species that culminate in fungal zinc starvation and toxicity.^[9] Thus, GM-CSF facilitates development of the immune system and promotes defense against infections.^{[citation needed]}

GM-CSF also plays a role in embryonic development by functioning as an embryokine produced by reproductive tract.^[10]

Genetics

The human gene has been localized in close proximity to the

Human granulocyte-macrophage colony-stimulating factor is glycosylated in its mature form.^[citation needed]

History

GM-CSF was first cloned in 1985, and soon afterwards three potential drug products were being made using recombinant DNA technology: molgramostim was made in Escherichia coli and is not glycosylated, sargramostim was made in yeast, has a leucine instead of proline at position 23 and is somewhat glycosylated, and regramostim was made in Chinese hamster ovary cells (CHO) and has more glycosylation than sargramostim. The amount of glycosylation affects how the body interacts with the drug and how the drug interacts with the body.^[13]

At that time,

Molgramostim was eventually co-developed and co-marketed by Novartis and Schering-Plough under the trade name Leucomax for use in helping white blood cell levels recover following chemotherapy, and in 2002 Novartis sold its rights to Schering-Plough.[17]^[18]

Sargramostim was approved by the US FDA in 1991 to accelerate white blood cell recovery following autologous

Imlygic was approved by the US FDA in October 2015,[20] and in December 2015 by the EMA, as an oncolytic virotherapy, commercialized by Amgen Inc. This oncolytic herpes virus, named Talimogene laherparepvec, has been genetically engineered to express human GM-CSF using the tumor cells machinery.^[21]

Clinical significance

GM-CSF is found in high levels in joints with rheumatoid arthritis and blocking GM-CSF as a biological target may reduce the inflammation or damage. Some drugs (e.g. otilimab) are being developed to block GM-CSF.^[22] In critically ill patients GM-CSF has been trialled as a therapy for the immunosuppression of critical illness, and has shown promise restoring monocyte^[23] and neutrophil^[24] function, although the impact on patient outcomes is currently unclear and awaits larger studies.

GM-CSF stimulates

Monoclonal antibodies against GM-CSF are being used as treatment in clinical trials against rheumatoid arthritis, ankylosing spondylitis, and COVID-19.^[25]

See also

• CFU-GM
• Filgrastim (Neupogen, a granulocyte colony-stimulating factor (G-CSF) analog)
• Granulocyte-macrophage colony-stimulating factor receptor
• Lenzilumab
• PEGylated form filgrastim
  )