遺伝子組換えヒト顆粒球増殖因子 (G-CSF) の癌治療への応用

抄録

Recombinant human granulocyte colony-stimulating factor (Re Hu G-CSF) was prepared and its stimulating effect on granulocytopoiesis was examined in mice. Human G-CSF was purified to homogeneity from conditioned media of a G-CSF producing cell line. The amino-terminal sequence was determined. By using oligonucleotides as probes, which were proposed by the amino acid sequence, a cDNA library preparcd from human macrophages was screened. The cloned G-CSF cDNA was expresscd in E. coli K12MM294, and the mature protein was purified to homogeneity. Mice were given intraperitoneal injections of Re Hu G-CSF everyday for 14 days. Peripheral blood granulocyte counts were examined after 4, 8, 12, and 14 days of injection. Mice were sacrificed on the 14th day for histologic examinations of bone marrow, and spleen. Granulocyte counts began to increase on the 4th day and reached about 80, 000/mm on the 14th day. Cells of granulocyte lineage were markedly increased in the bone marrow and spleen. Granulocyte precursors (CFU-C) were remarkably increased in the spleen. When mice were treated with 5-fluorouracil, cyclophosphamide, or irradiation, the period of granulocytopenia was significantly shortened by subcutaneous injections of Re Hu G-CSF.
These results suggest that human G-CSF play a central role in granulocyte production in vivo. The ability of Re Hu G-CSF to stimulate granulocyte production implies that this factor will be clinically useful in neutropenic patients treated with anti-cancer agents or irradiation.