In vivo effect of human granulocyte colony-stimulating factor derivatives on hematopoiesis in primates.
Using cynomolgus monkeys, we studied the hematopoietic effect and antigenicity of the human granulocyte colony-stimulating factor (hG-CSF) derivatives mutated at N-terminal amino acids (NC-59 and KW-2228) and that lacking N-terminal amino acids (M-7) in comparison with intact hG-CSF. These compounds were subcutaneously administered daily into the back of cynomolgus monkeys at the doses of 1 and 100 micrograms/kg for 2 weeks, and withdrawn for 2 weeks (1st course). After that, the same schedule was repeated (2nd course), and intact hG-CSF and KW-2228 were further administered for 2 weeks (3rd course). In the first course, all of the G-CSF derivatives showed excellent dose-dependent granulopoietic activities. In the 2nd course, however, the activities of NC-59 and M-7 were decreased and the elevations of binding and neutralizing antibody titers were observed. On the other hand, KW-2228 showed granulopoietic activities equal to or better than that of intact hG-CSF and had low antibody titer throughout all the courses.
Kato
Y
Y
Kyowa Bio-Research Laboratories Co., Ltd., Yamaguchi, Japan.
Yamamoto
M
M
Ikenaga
T
T
Shintome
T
T
Asano
M
M
Okabe
M
M
Hara
T
T
Deguchi
T
T
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000097:blood; D000939:Epitopes / Q000276:immunology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D006410:Hematopoiesis; D006801:Humans; D007700:Kinetics; D007958:Leukocyte Count; D008252:Macaca fascicularis; D008297:Male; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology
D000906:Antibodies; D000939:Epitopes; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor