公开(公告)号：US20030216295A1

公开(公告)日：2003-11-20

申请号：US10325606

申请日：2002-12-20

Applicant: La Jolla Cancer Research Foundation

Inventor： Minoru Fukuda ,  Ritsuko Sawada ,  Shigeru Tsuboi

IPC: A61K038/14 ,  C07H021/04 ,  C07K009/00 ,  C07K016/18 ,  C12P021/02 ,  C12N005/06

CPC classification number: C07K14/705 ,  A61K38/00 ,  C07K14/47

Abstract: 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.

Abstract translation: 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-选择蛋白的配体，包括唾液酸Lex糖蛋白，唾液酸Lex糖脂和唾液酸Le x低聚糖以及其它相关的唾液酸含Lex 能够抑制E-选择蛋白介导的细胞粘附于内皮细胞的分子。 本发明还提供能够阻断E-选择素介导的细胞粘附的唾液酸Le x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够产生唾液酸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Le x阳性糖蛋白，特别是唾液酸Le x阳性嵌合白血球蛋白的方法。