GM-CSF (Granulocyte Macrophage Colony Stimulating Factor)

Biology and Diseases

Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) is a cytokine produced by T cells, B cells, macrophages, mast cells and fibroblasts in response to inflammation or infection. Its primary role is to stimulate granulocyte and monocyte production in the bone marrow. Once GM-CSF has bound to its receptor, the activated complex propagates a signaling cascade that increases macrophage counts in order to fight infection. Thus increased GM-CSF can be observed during episodes of infectious disease and in a spectrum of inflammatory disorders. Conversely, a lack of GM-CSF resulting from autoantibody production has been linked to pulmonary alveolar proteinosis.

Therapies

Therapeutic use of GM-CSF has been investigated for pulmonary alveolar proteinosis, leukemia, neutropenia, breast cancer, hepatoma and Chron’s disease. A recombinant form of GM-CSF (sargramostim) is marketed under the trade name Leukine. The drug is prescribed to adult patients with acute myelogenous leukemia following chemotherapy treatments. GM-CSF is able to boost neutrophil recovery and decrease the risk of infection due to a weakened immune system. In clinical settings, GM-CSF has been shown to enhance myeloid growth in the case of bone marrow transplantation. Furthermore, a phase III clinical trial will soon be underway to examine the safety and efficacy of GM-CSF for treating melanoma.

Unmet Need

GM-CSF continues to prove its usefulness as a prognostic biomarker in cancer settings and has been shown to effectively relieve inflammation caused by an overactive immune system. However, establishing baseline concentrations from healthy subjects still remains an obstacle with currently available ELISA and multiplex assay technologies. Studies have suggested that existing assays are not able to statistically differentiate the concentrations of plasma GM-CSF between healthy and diseased individuals. The future of diagnostics requires a sensitive immunoassay capable of stratifying the transition from healthy to diseased states based on minute changes in GM-CSF concentrations.

Singulex Answer

The Singulex GM-CSF assay, optimized for use on the Erenna System, enables scientists to measure over a broad dynamic range of GM-CSF in plasma. The assay has an LLoQ of 0.14 pg/mL and a reading range of 0.04-1000 pg/mL, providing accurate quantification of GM-CSF from only 100mL of plasma.

This assay will allow investigators to:

1. Measure the efficacy and dosing of therapeutics designed to increase levels of GM-CSF, particularly in restoring neutrophil production in leukemic patients.

2. Measure decreased concentrations of GM-CSF in patients with pulmonary alveolar proteinosis, which are below levels found in healthy subjects.

3. Design more robust clinical and preclinical studies when GM-CSF concentration is used as a therapeutic endpoint.

4. Understand how GM-CSF concentrations change in patients as they transition from healthy to diseased states.

Application Note

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