GM-CSF

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Ligands
GM-CSF (Human)

GtoPdb Ligand ID: 4942

Synonyms: colony-stimulating factor | CSF

Compound class: Endogenous peptide in human, mouse or rat

Comment: GM-CSF as a target in inflammatory/autoimmune disease was reviewed by Hamilton (2015) [3].

COVID-19: In March 2021, results of the analysis of the inflammatory cytokine/chemokine profiles from COVID-19 patients (spanning the spectrum from mild to fatal disease) and archival samples from patients with severe influenza, identified elevated GM-CSF as a principal marker of severe COVID-19 immunopathology. Both IL-6 and GM-CSF elevations were detected as potent drivers of COVID-19 pathogenesis (associated with disease severity and coinciding with elevated markers of endothelial injury and thrombosis), GM-CSF distinguished COVID-19 from fatal influenza [8]. The findings from this study supports continued targeting of GM-CSF as a therapy for patients with severe COVID-19. Investigational anti-GM-CSF monoclonals that were repositioned for COVID-19 and entered into clinical trials in COVID-19 positive patients include lenzilumab, gimsilumab, otilimab and plonmarlimab [2].

Species: Human

References
1. Bebbington CR, Yarranton GT. (2011) Methods of treating heart failure using an anti-GM-CSF antibody. Patent number: US8075885 B2. Assignee: Kalobios Pharmaceuticals, Inc.. Priority date: 01/12/2015. Publication date: 13/12/2011.
2. Bonaventura A, Vecchié A, Wang TS, Lee E, Cremer PC, Carey B, Rajendram P, Hudock KM, Korbee L, Van Tassell BW et al.. (2020) Targeting GM-CSF in COVID-19 Pneumonia: Rationale and Strategies. Front Immunol, 11: 1625. [PMID:32719685]
3. Hamilton JA. (2015) GM-CSF as a target in inflammatory/autoimmune disease: current evidence and future therapeutic potential. Expert Rev Clin Immunol, 11 (4): 457-65. [PMID:25748625]
4. Holgate ST. (2000) Epithelial damage and response. Clin Exp Allergy, 30 Suppl 1: 37-41. [PMID:10849473]
5. Krinner EM, Raum T, Petsch S, Bruckmaier S, Schuster I, Petersen L, Cierpka R, Abebe D, Mølhøj M, Wolf A et al.. (2007) A human monoclonal IgG1 potently neutralizing the pro-inflammatory cytokine GM-CSF. Mol Immunol, 44 (5): 916-25. [PMID:16697465]
6. Sass PM, Nicolaides NE, Grasso L, Li J, Chao Q, Routhier E, Ebel W. (2007) Antigenic gm-csf peptides and antibodies to gm-csf. Patent number: WO2007092939. Assignee: Morphotek, Inc.. Priority date: 08/02/2006. Publication date: 16/08/2007.
7. Steidl S, Thomassen-Wolf E. (2006) Anti-gm-csf antibodies and uses therefor. Patent number: WO2006122797A2. Assignee: Morphosys Ag. Priority date: 18/05/2005. Publication date: 23/11/2006.
8. Thwaites RS, Sanchez Sevilla Uruchurtu A, Siggins MK, Liew F, Russell CD, Moore SC, Fairfield C, Carter E, Abrams S, Short CE et al.. (2021) Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19. Sci Immunol, 6 (57). DOI: 10.1126/sciimmunol.abg9873 [PMID:33692097]
9. Uddin M, Lau LC, Seumois G, Vijayanand P, Staples KJ, Bagmane D, Cornelius V, Dorinsky P, Davies DE, Djukanović R. (2013) EGF-induced bronchial epithelial cells drive neutrophil chemotactic and anti-apoptotic activity in asthma. PLoS ONE, 8 (9): e72502. [PMID:24039773]
10. Wang Z, Fang L, Guo B, Zang J. (2018) Anti-gm-csf antibodies and uses thereof. Patent number: WO2018050111A1. Assignee: I-Mab. Priority date: 09/09/2016. Publication date: 22/03/2018.

References

1. Bebbington CR, Yarranton GT. (2011)
Methods of treating heart failure using an anti-GM-CSF antibody.
Patent number: US8075885 B2. Assignee: Kalobios Pharmaceuticals, Inc.. Priority date: 01/12/2015. Publication date: 13/12/2011.

2. Bonaventura A, Vecchié A, Wang TS, Lee E, Cremer PC, Carey B, Rajendram P, Hudock KM, Korbee L, Van Tassell BW et al.. (2020)
Targeting GM-CSF in COVID-19 Pneumonia: Rationale and Strategies.
Front Immunol, 11: 1625. [PMID:32719685]

3. Hamilton JA. (2015)
GM-CSF as a target in inflammatory/autoimmune disease: current evidence and future therapeutic potential.
Expert Rev Clin Immunol, 11 (4): 457-65. [PMID:25748625]

4. Holgate ST. (2000)
Epithelial damage and response.
Clin Exp Allergy, 30 Suppl 1: 37-41. [PMID:10849473]

5. Krinner EM, Raum T, Petsch S, Bruckmaier S, Schuster I, Petersen L, Cierpka R, Abebe D, Mølhøj M, Wolf A et al.. (2007)
A human monoclonal IgG1 potently neutralizing the pro-inflammatory cytokine GM-CSF.
Mol Immunol, 44 (5): 916-25. [PMID:16697465]

6. Sass PM, Nicolaides NE, Grasso L, Li J, Chao Q, Routhier E, Ebel W. (2007)
Antigenic gm-csf peptides and antibodies to gm-csf.
Patent number: WO2007092939. Assignee: Morphotek, Inc.. Priority date: 08/02/2006. Publication date: 16/08/2007.

7. Steidl S, Thomassen-Wolf E. (2006)
Anti-gm-csf antibodies and uses therefor.
Patent number: WO2006122797A2. Assignee: Morphosys Ag. Priority date: 18/05/2005. Publication date: 23/11/2006.

8. Thwaites RS, Sanchez Sevilla Uruchurtu A, Siggins MK, Liew F, Russell CD, Moore SC, Fairfield C, Carter E, Abrams S, Short CE et al.. (2021)
Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19.
Sci Immunol, 6 (57). DOI: 10.1126/sciimmunol.abg9873 [PMID:33692097]

9. Uddin M, Lau LC, Seumois G, Vijayanand P, Staples KJ, Bagmane D, Cornelius V, Dorinsky P, Davies DE, Djukanović R. (2013)
EGF-induced bronchial epithelial cells drive neutrophil chemotactic and anti-apoptotic activity in asthma.
PLoS ONE, 8 (9): e72502. [PMID:24039773]

10. Wang Z, Fang L, Guo B, Zang J. (2018)
Anti-gm-csf antibodies and uses thereof.
Patent number: WO2018050111A1. Assignee: I-Mab. Priority date: 09/09/2016. Publication date: 22/03/2018.