Phase II year
1987
(last award dollars: 1988)
Human granulocyte-macrophage colony stimulating factor (GM-CSF) is a hematopoietic growth factor that primarily stimulates the growth and development of granulocytes and macrophages and, of less certain significance, platelets and red blood cell precursors in vitro. GM-CSF has also been shown to have similar effects on hematopoiesis in primate model systems. This suggests a potential for clinical use in stimulating the more rapid return of white blood cell levels to normal in patients treated with chemotherapy.Currently, a proprietary system for the production of GM-CSF in filamentous fungus is being used to produce GM-CSF. The efficacy of the native, carbohydrate-free GM-CSF produced in this system will be compared to rGM-CSF made by mammalian cells in a primate model system. This model system will be used to determine the role of carbohydrate in the circulatory half-life, antigenicity, toxicity, and efficacy of GM-CSF. Different portions of the amino acid sequence of GM-CSF will also be tested to determine whether a subset or altered-sequence form of GM-CSF may be developed that would be a more effective therapeutic agent. Expression of GM-CSF will be optimized to commercial production levels, and a large-scale purification scheme will be developed.National Institute of Allergy and Infectious Diseases (NIAID)