G-CSF (Granulocyte Colony Stimulating Factor)

Biology and Diseases

Granulocyte-Colony Stimulating Factor (G-CSF) is an endogenous hematopoietic agent activated and expressed by many types of cells, including macrophages, tumor cells, fibroblasts and endothelial cells. One of the main functions of G-CSF is to regulate formation of neutrophils during hematopoiesis, which are important for proper immune function. For example, in cancer patients, reduced hematopoeisis from chemotherapy results in low neutrophil production, which jeopardizes the immune system, leaving the body susceptible to infectious attacks.

Therapies

G-CSF has been the focus of pharmaceutical development for several decades. A recombinant human G-CSF (filgrastim) was marketed under the trade name Neupogen in 1991. In 2002, Neulasta (pegfilgrastim) was released as the longer-lasting form of Neupogen. A third form of G-CSF (lenograstim), expressed in Chinese Hamster Ovary cells instead of E. coli as in the former two, is also available on the market. G-CSF therapy has been shown to restore hematopoiesis in cancer and leukemic patients by stimulating white blood cell production. Interestingly, G-CSF has also demonstrated effectiveness in improving cardiac function following a myocardial infarction.

Unmet Need

The efficacy in reducing the risk of infection following cancer treatments with G-CSF has been well established, but its direct therapeutic effect still remains unanswered. Ongoing investigations of the prognostic use of this growth factor require an assay capable of differentiating G-CSF concentrations in healthy and diseased individuals across a broad quantification range. A leukemia treatment study reported that the level of G-CSF in chronic phase patients is either low (0.9 pg/mL) or undetectable, and is much lower than that found in normal controls (22 pg/mL). Thus it is imperative to have an assay with improved sensitivity and accuracy over a spectrum of sample concentrations in order to successfully evaluate effectiveness and monitor the dosing of potential G-CSF treatments.

Singulex Answer

The Singulex G-CSF assay, optimized for use on the Erenna System, enables scientists to measure a broad dynamic range of G-CSF in plasma. The assay has an LLoQ of 0.20 pg/mL and a reading range of 0.14-100 pg/mL, providing accurate quantification of G-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 G-CSF, particularly in rescuing hematopoiesis in leukemic patients.

2. Accurately quantify below-normal levels of G-CSF compared to healthy subjects, such as in cases of neutropenia in chronic phase cancer patients.

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

4. Establish baseline concentrations in healthy subjects and monitor changes in G-CSF levels during disease progression.

Application Note

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