公开(公告)号：US4760021A

公开(公告)日：1988-07-26

申请号：US668904

申请日：1984-11-07

申请人： Akio Mimura ,  Kaoru Yoshinari ,  Katsumi Yuasa ,  Tsuneo Sato

发明人： Akio Mimura ,  Kaoru Yoshinari ,  Katsumi Yuasa ,  Tsuneo Sato

IPC分类号： A61K38/00 ,  A61K35/12 ,  A61K38/16 ,  A61P7/00 ,  A61P35/02 ,  C07K14/475 ,  C12P21/00 ,  A61K37/02 ,  C07K3/02

CPC分类号： C07K14/475

摘要： There is provided a proteinaceous biological response modifier having the following properties: (a) molecular weight: 35,000 to 65,000; (b) isoelectric point: 5.0 to 6.1; (c) physiological action on human leukemia cells: to induce human leukemia to differentiate into macrophage-like cells; (d) physiological action on myeloid leukemia cells from mice: to induce myeloid leukemia cells from mice to differentiate into macrophage-like cells; (e) affinity to Concanavalin A Sepharose: not adsorbed; (f) affinity to Blue Sepharose Resin: not adsorbed; (g) pH-stability and thermostability: substantially not inactivated at pH 2 to 10, at 2.degree. C. for 6 hours; not inactivated at 56.degree. C. for 60 minutes; but inactivated by 30% at 70.degree. C. for 60 minutes; (h) sensitivity to enzymes: not inactivated by deoxyribonuclease; not inactivated by glycosidase; and inactivated by protease; (i) flow cytometry analysis: to concentrate cell division cycle of human leukemia cells to G.sub.0 /G.sub.1 phase. There is also provided a process for the production of the proteinaceous biological response modifier comprising culturing human leukemia cells in a differentiation medium in the presence of a substance capable of inducing the human leukemia cells to differentiate into macrophage-like cells; separating the macrophage-like cells from the culture medium; activating the macrophage-like cells in a production medium by a mitogen to enhance the production of the proteinaceous biological response modifier; and isolating the proteinaceous biological response modifier from the production medium.The biological response modifier has anti-tumor activity.

摘要翻译： 提供具有以下性质的蛋白质生物反应调节剂：（a）分子量：35,000至65,000; （b）等电点：5.0〜6.1; （c）人类白血病细胞的生理作用：诱导人类白血病分化为巨噬细胞样细胞; （d）来自小鼠的骨髓性白血病细胞的生理作用：从小鼠诱导骨髓性白血病细胞分化成巨噬细胞样细胞; （e）对伴刀豆球蛋白A琼脂糖的亲和力：未吸附; （f）对蓝色琼脂糖树脂的亲和力：未吸附; （g）pH稳定性和热稳定性：基本上未在2℃灭菌2℃，6小时; 未在56℃灭活60分钟; 但在70℃下灭活30％60分钟; （h）对酶的敏感性：未被脱氧核糖核酸酶灭活; 不被糖苷酶灭活; 并通过蛋白酶灭活; （i）流式细胞术分析：将人白血病细胞的细胞分裂周期集中到G0 / G1期。 还提供了一种用于生产蛋白质生物反应调节剂的方法，其包括在能够诱导人白血病细胞分化成巨噬细胞样细胞的物质存在下，在分化培养基中培养人白血病细胞; 从培养基中分离巨噬细胞样细胞; 通过有丝分裂原激活生产培养基中的巨噬细胞样细胞以增强蛋白质生物反应调节剂的产生; 并从生产培养基中分离蛋白质生物反应调节剂。 生物反应调节剂具有抗肿瘤活性。