A Novel Recombinant Human Granulocyte Colony-Stimulating Factor (G-CSFa) Enhances Peripheral Platelet Recovery in Mice Exposed to adiotherapy and Has No Immunogenicity in Rats

Abstract

Using site-direct mutagenesis and recombinant DNA technology, we had previously obtained a structurally modified derivative of human G-CSF termed G-CSFa. G-CSFa contains alanine 17 (instead of cysteine 17 as in wildtype G-CSF) as well as four additional amino acids (methionine, arginine, glycine and serine) at the amino terminus. Previous studies showed that G-CSFa is more potent than the wild-type counterpart in stimulating proliferation and differentiation of myeloid cells of the granulocytic lineage, both in vitro and in vivo. Here, we show that G-CSFa can significantly accelerate peripheral platelet recovery in C57BL/6 mice exposed to radiotherapy. We further demonstrate that G-CSFa is not immunogenic in rats, by confirming the absence of any binding antibodies, analyzed using ELISA, or neutralizing antibodies, determined using the NFS-60 cell proliferation bioassay, to G-CSFa in the sera of Sprague-Dawley rats following repeated G-CSFa administration. Taken together, these findings further support the benefits of G-CSFa for clinical therapy.