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    • 39. 发明授权
    • Leukosialin: Ig fusion proteins
    • 白细胞介素:Ig融合蛋白
    • US06537553B1
    • 2003-03-25
    • US08369754
    • 1995-01-06
    • Minoru FukudaRitsuko SawadaShigeru Tsuboi
    • Minoru FukudaRitsuko SawadaShigeru Tsuboi
    • C12P2100
    • C07K14/705A61K38/00C07K14/47
    • The present invention provides antagonists to cell adhesion useful in controlling the negative effects of inflammation, and the metastasis of cancer cells. These antagonists are ligands to E-selectin containing the sialyl Lex structure, including sialyl Lex glycoproteins, sialyl Lex glycolipids, and sialyl Lex oligsaccharides, and other related sialyl Lex-containing molecules capable of inhibiting E-selectin mediated cell adhesion to endothelial cells. The present invention also provides antibodies against sialyl Lex determinants capable of interrupting E-selectin mediated cell adhesion, which are also considered antagonists according to the present invention. The present invention also provides methods of using the antagonists of the present invention to reduce inflammation, and methods to inhibit the process of metastasis by carcinogenic cells. The present invention also provides nucleic acid molecules encoding the glycoprotein antagonists of the present invention, in particular soluble chimeric leukosialin, and vectors capable of expressing these nucleic acid molecules, as well as cells capable of producing sialyl Lex positive recombinant glycoproteins. The present invention further provides a method of determining metastatic potential by comparing the efficiency of E-selectin-mediated adhesion of cell samples. In addition the present invention provides a method of producing a preferred antagonist of the present invention, sialyl Lex positive glycoproteins, in particular, sialy Lex positive chimeric leukosialin.
    • 本发明提供了可用于控制炎症的负面作用和癌细胞转移的细胞粘附的拮抗剂。 这些拮抗剂是含有唾液酸Lex结构的E-选择素的配体,包括唾液酸Lex糖蛋白,唾液酸Lex糖脂和唾液酸Lex低聚糖,以及能够抑制E-选择蛋白介导的细胞粘附于内皮细胞的其它相关唾液酸含Lex分子。 本发明还提供能够中断E-选择蛋白介导的细胞粘附的唾液酸基决定簇的抗体,其也被认为是根据本发明的拮抗剂。 本发明还提供了使用本发明的拮抗剂来减少炎症的方法,以及抑制致癌细胞转移过程的方法。 本发明还提供编码本发明的糖蛋白拮抗剂,特别是可溶性嵌合白血球蛋白的核酸分子,以及能够表达这些核酸分子的载体,以及能产生唾液酸Lex阳性重组糖蛋白的细胞。 本发明还提供了通过比较E-选择蛋白介导的细胞样品粘附的效率来确定转移潜能的方法。 此外,本发明提供了制备本发明优选的拮抗剂,唾液酸Lex阳性糖蛋白,特别是唾液酸Lex阳性嵌合白血球蛋白的方法。