Neutrophil Biology and the Next Generation of Myeloid Growth Factors

Neutrophils are the body's critical phagocytic cells for defense against bacterial and fungal infections; bone marrow must produce approximately 10 x 109 neutrophils/kg/d to maintain normal blood neutrophil counts. Production of neutrophils depends on myeloid growth factors, particularly granulocyte colony-stimulating factor (G-CSF). After the original phase of development, researchers modified these growth factors to increase their size and delay renal clearance, increase their biologic potency, and create unique molecules for business purposes. Pegylated G-CSF is a successful product of these efforts. Researchers have also tried to identify small molecules to serve as oral agents that mimic the parent molecules, but these programs have been less successful. In 2006, the European Medicines Agency established guidelines for the introduction of new biologic medicinal products claimed to be similar to reference products that had previously been granted marketing authorization in the European community, called bio-similars. Globally, new and copied versions of G-CSF and other myeloid growth factors are now appearing. Some properties of the myeloid growth factors are similar to other agents, offering opportunities for the development of alternative drugs and treatments. For example, recent research shows that hematopoietic progenitor cells can be mobilized with a chemokine receptor antagonist, chemotherapy, G-CSF, and granulocyte macrophage colony-stimulating factor. Advances in neutrophil biology coupled with better understanding and development of myeloid growth factors offer great promise for improving the care of patients with cancer and many other disorders.

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Dr. Dale is a consultant for Amgen Inc.; Caremark LLC; Cellerant Therapeutics, Inc.; Merck & Co., Inc.; Maxygen, Inc.; Schering-Plough Corporation; and Telik, Inc. He receives research support from Amgen Inc., Merck & Co., Inc., The Barth Syndrome Foundation, Inc., Genzyme Corporation, and National Institutes of Health; and is a speaker for Amgen Inc. Correspondence: David C. Dale, MD, Department of Medicine, University of Washington Medical Center, 1959 NE Pacific Street, Room AA522, Box 356422, Seattle, WA 98195-6422.E-mail: dcdale@u.washington.edu
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