October 4, 2022

Pulmonary Alveolar Proteinosis Refractory to Plasmapheresis and Rituximab despite GM-CSF Antibody Reduction

We share our experience of a patient with pulmonary alveolar proteinosis who was refractory to plasmapheresis and rituximab despite a significant reduction in the offending antibody. He presented with shortness of breath, fevers, chills, and sweats for 4 months. He was diagnosed with autoimmune PAP based on typical radiology findings, bronchoalveolar fluid analysis, and elevated anti-GM-CSF levels.
Given his limited improvement with whole lung lavage and inhaled GM-CSF therapy, he underwent two series of plasmapheresis. Series one was 5 procedures in 6 days, and series two was 5 procedures in 9 days followed by rituximab. These did not appear to provide any lasting clinical benefit in the year after plasmapheresis despite a marked decrease in serum anti-GM-CSF levels. However, about a year after plasmapheresis, he went into remission and has not required any treatment.

A meta-analysis of granulocyte-macrophage colony-stimulating factor (GMCSFantibody treatment for COVID-19 patients

Objective: This meta-analysis aims to assess the efficacy and safety of granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies on COVID-19.
Methods: Relevant literatures about GM-CSF antibody treatment in COVID-19 patients were searched from the PubMed, Cochrane Library, Embase, Google scholar, and Baiduscholar databases from the COVID-19 outbreak in December 2019 until 1 January 2021. The primary outcomes included the death, intensive care unit (ICU) admission risk, ventilation requirement, and secondary infection.
Results: A total of 12 eligible literature involving 8979 COVID-19 patients were recruited, and they were divided into experimental group (n = 2673) and control group (n = 6306). Using a random-effect model, it is found that the GM-CSF antibody treatment was associated with a 23% decline of the risk of death [odd’s ratio (OR): 0.34, 95% confidence interval (CI): 0.21-0.56, p < 0.0001] and a 20% enhancement of ventilation (OR: 1.47, 95% CI: 1.19, 1.80, p = 0.0002). GM-CSF antibody treatment did not have a significant correlation to secondary infection and increased risk of ICU admission in COVID-19 patients, which may be attributed to the older age and the length of stay.
Conclusions: Severe COVID-19 patients can benefit from GM-CSF antibodies.

Monoclonal antibodies capable of binding SARS-CoV-2 spike protein receptor-binding motif specifically prevent GMCSF induction

A severe acute respiratory syndrome (SARS)-like coronavirus 2 (SARS-CoV-2) has recently caused a pandemic COVID-19 disease that infected approximately 94 million and killed more than 2,000,000 people worldwide. Like the SARS-CoV, SARS-CoV-2 also employs a receptor-binding motif (RBM) of its envelope spike protein for binding the host angiotensin-converting enzyme 2 (ACE2) to gain viral entry. Currently, extensive efforts are being made to produce vaccines against a surface fragment of a SARS-CoV-2, such as the spike protein, in order to boost protective antibodies that can inhibit virus-ACE2 interaction to prevent viral entry.
It was previously unknown how spike protein-targeting antibodies would affect innate inflammatory responses to SARS-CoV-2 infections. Here we generated a highly purified recombinant protein corresponding to the RBM of SARS-CoV-2, and used it to screen for cross-reactive monoclonal antibodies (mAbs). We found two RBM-binding mAbs that competitively inhibited its interaction with human ACE2, and specifically blocked the RBM-induced GM-CSF secretion in both human peripheral blood mononuclear cells and murine macrophage cultures. Our findings have suggested a possible strategy to prevent SARS-CoV-2-elicited “cytokine storm,” and revealed a potentially anti-inflammatory and protective mechanism for SARS-CoV-2 spike-based vaccines.

Monoclonal Antibodies Capable of Binding SARS-CoV-2 Spike Protein Receptor Binding Motif Specifically Prevent GMCSF Induction

A severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) has recently caused a pandemic COVID-19 disease that infected more than 25.6 million and killed 852,000 people worldwide. Like the SARS-CoV, SARS-CoV-2 also employs a receptor-binding motif (RBM) of its envelope spike protein for binding the host angiotensin-converting enzyme 2 (ACE2) to gain viral entry. Currently, extensive efforts are being made to produce vaccines against a surface fragment of a SARS-CoV-2, such as the spike protein, in order to boost protective antibody responses. It was previously unknown how spike protein-targeting antibodies would affect innate inflammatory responses to SARS-CoV-2 infections.
Here we generated a highly purified recombinant protein corresponding to the RBM of SARS-CoV-2, and used it to screen for cross-reactive monoclonal antibodies (mAbs). We found two RBM-binding mAbs that competitively inhibited its interaction with human ACE2, and specifically blocked the RBM-induced GM-CSF secretion in both human monocyte and murine macrophage cultures. Our findings have suggested a possible strategy to prevent SARS-CoV-2-elicited “cytokine storm”, and provided a potentially useful criteria for future assessment of innate immune-modulating properties of various SARS-CoV-2 vaccines.

High Levels of Anti-GMCSF Antibodies in Deep Infiltrating Endometriosis.

  • Endometriosis is a chronic hormono-dependent inflammatory gynecological disease. Endometriosis can be subdivided into three forms: superficial peritoneal implants, endometrioma, and deep infiltrating endometriosis (DIE). Inflammation is a typical feature of endometriosis with overproduction of prostaglandins, chemokines, and cytokines, like granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF is a hematopoietic growth factor and immune modulator which belongs to the group of cytokines that actively participate in inflammatory reactions. GM-CSF autoantibodies (Ab) are described in inflammatory diseases such as Crohn disease and ulcerative colitis where high concentrations of anti-GM-CSF Ab are correlated with severity, complications, and relapses.
  • We have evaluated the presence of anti-GM-CSF Ab in the serum of 106 patients with endometriosis and 92 controls using a home-made enzyme-linked immunosorbent assay (ELISA) and correlated the results with the form and severity of the disease. We found that anti-GM-CSF Ab level is significantly increased in the sera of patients with endometriosis compared to controls and is associated with the severity of the disease especially in patients with deep endometriosis (p < 0.0001) with the highest number of lesions (p = 0.0034), including digestive involvement (p = 0.0041).
  • We also found a correlation between these levels of anti-GM-CSF Ab and the number of lesions in DIE patients (r = 0.913). In this way, searching anti-GM-CSF Ab in endometriosis patient sera could be of value for patient follow-up and put further insight into the role of inflammation and of GM-CSF in endometriosis pathogenesis.

Mouse GM-CSF ELISA Kit, 96 tests, Quantitative

MGM-CSF-100 Alpha Diagnostics 1 kit 482 EUR

Human GM-CSF ELISA Kit, 96 tests, Quantitative

HGM-CSF-100 Alpha Diagnostics 1 kit 482 EUR

PRE-GMP rHu GM-CSF, Molgramostim-Leukoma

04-RHUGM-CSF-7A10 Gentaur Genprice 300 µg 385 EUR

GM-CSF

E21-003 EnoGene 10ug 343 EUR

GM-CSF

E21-J46 EnoGene 10ug 343 EUR

Filgrastim (rHuG-CSF)

rHuG-CSF Amyotop 300µg/vial 225 EUR

Molgramostim (rHuGM-CSF)

rHuGM-CSF Amyotop 300µg/vial 249 EUR

GM-CSF, Human

HY-P7016A MedChemExpress 50ug 441 EUR

GM-CSF, Mouse

HY-P7361 MedChemExpress 50ug 497 EUR

GM-CSF/CSF2

E21-C79 EnoGene 10ug 343 EUR

His-GM-CSF

E13-010-1 EnoGene 10μg 291 EUR

His-GM-CSF

E13-010-2 EnoGene 50μg 700 EUR

GM - CSF Human

PR27068 Neuromics 2 ug 191 EUR

GM - CSF Rat

PR27071 Neuromics 2 ug 148 EUR

GM - CSF Sf9

PR27072 Neuromics 2 ug 148 EUR

GM - CSF Mouse

PR27074 Neuromics 2 ug 191 EUR

rHu GM-CSF

AK9707-0005 Akron Biotech 5µg Ask for price

rHu GM-CSF

AK9707-0020 Akron Biotech 20µg Ask for price

rHu GM-CSF

AK9707-0100 Akron Biotech 100µg Ask for price

rHu GM-CSF

AK9707-1000 Akron Biotech 1mg Ask for price

GM-CSF, Human

LF-P0278 Abfrontier 10 ug 270 EUR

GM-CSF, Human

LF-P0278A Abfrontier 100 ug 1811 EUR

GM-CSF antibody

70-GR30 Fitzgerald 50 ug 298 EUR

GM-CSF antibody

70R-GR026 Fitzgerald 50 ug 273 EUR

GM-CSF protein

30R-AG014 Fitzgerald 5 ug 133 EUR

GM-CSF protein

30R-AG016 Fitzgerald 50 ug 529 EUR

GM-CSF protein

30R-AG022 Fitzgerald 20 ug 273 EUR

anti-GM-CSF

YF-PA11125 Abfrontier 100 ug 403 EUR

Increased Tim-3 expression on TILs during treatment with the Anchored GMCSF vaccine and anti-PD-1 antibodies is inversely correlated with response in prostate cancer.

Programmed death receptor-1 (PD-1) and T cell immunoglobulin and mucin domain-containing protein-3 (Tim-3) play important roles in tumor immune evasion. PD-1 blockade could produce an effective antitumor effect in many solid tumors except prostate cancer (PCa) because of rare programmed death ligand-1 (PD-L1) expression on PCa cells. Streptavidin (SA)-GM-CSF surface-anchored tumor cell (Anchored GM-CSF) vaccines could increase the number of tumor-infiltrating lymphocytes (TILs) and induce specific antitumor immune responses. The Anchored-GM-CSF vaccine and anti-PD-1 antibodies exerted synergistic effects in mouse models of PCa metastasis. However, the response rate was low due to the presence of other negative regulatory pathways.
Tim-3 expression could be upregulated at resistance to combination therapy with anti-PD-1 antibodies and the Anchored GM-CSF vaccine. Sequential administration of anti-PD-1 and anti-Tim-3 antibodies could further improve the efficacy of the Anchored GM-CSF vaccine therapy, and tumor regression was noted in over 60% of animals. This triple therapy improved the specific cytotoxic activity, proliferation and secretion of CD8+ TILs and reduced the production of tumor-promoting cytokines. These findings indicated that this triple therapy could induce a robust antitumor immune response in mouse models of PCa.

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