Large-scale production of hematopoietic growth factors

Genetic engineering has given us the means to produce large quantities of hematopoietic growth factors for clinical evaluation as therapeutic agents. The production technology for exploiting advances in genetic engineering is itself a new and rapidly evolving field of endeavor that has added another layer of choice for production. Commercial manufacturers of growth factors are now faced with an ever-expanding variety of alternatives in primary production systems, from E. coli to transgenic cows and a variety of choices in separation technologies for the isolation of these factors in a pharmaceutically acceptable form. Overlaying this plethora of options is the possibility of using site-specific mutagenesis to change the natural structure of growth factors to produce new chemical entities with novel pharmaceutical properties. For example, soluble forms of M-CSF have been created by specific deletion of hydrophobic transmembrane regions of the molecule and improved forms of G-CSF have been claimed to have been synthesized by directed amino acid substitution. The utility of these approaches will ultimately be decided by the relative efficacy of each product in the clinic and to a lesser extent process economics in the commercial marketplace.