Recombinant human granulocyte macrophage-colony stimulating factor expressed in yeast (sargramostim): A potential ally to combat serious infections

Clin Immunol. 2020 Jan;210:108292. doi: 10.1016/j.clim.2019.108292. Epub 2019 Oct 30.

Abstract

Granulocyte-macrophage-colony stimulating factor (GM-CSF), can direct the activation, proliferation and differentiation of myeloid-derived cells. It is also responsible for maturation and function of professional antigen presenting cells thereby impacting adaptive immune responses, while assisting to maintain epithelial barrier function. GM-CSF in combination with other endogenous cytokines and secondary stimuli, such as tumor necrosis factor can modulate pro-inflammatory monocyte priming via chromatin remodeling and enhanced transcriptional responses, a concept termed "trained immunity". An increase in the incidence of opportunistic fungal infections was recently reported in patients with hematological cancers receiving treatment with the BTK inhibitor, Ibrutinib. Tec Kinase BTK is known to influence the expression of GM-CSFRα and regulates downstream signaling pathways, suggesting a role for GM-CSF in maintenance of defense against fungal infections in immune competent hosts. Further examination of the potential mechanism(s) of action for naturally occurring GM-CSF and recombinant human GM-CSF (rhu-GM-CSF) expressed in yeast (sargramostim) are reviewed.

Keywords: Chronic refractory intracellular pathogens; GM-CSF; Immune response.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Chromatin Assembly and Disassembly / drug effects
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use
  • Humans
  • Immunity / drug effects
  • Immunomodulation
  • Immunotherapy / methods*
  • Infections / immunology
  • Infections / therapy*
  • Inflammation
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / therapeutic use
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Tumor Necrosis Factor-alpha / therapeutic use

Substances

  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • sargramostim
  • Granulocyte-Macrophage Colony-Stimulating Factor