INHIBITION OF CELL ADHESION BY CHEMICALLY-DEFINED OLIGOSACCHARIDES, THEIR DERIVATIVES, MIMETICS, AND ANTIBODIES DIRECTED THERETO

摘要

2129987 9317033 PCTABS00025 Many tumor-associated and leukocyte-associated carbohydrate antigens function as adhesion molecules, recognized by lectins (carbohydrate-protein interaction) or complementary carbohydrates (carbohydrate-carbohydrate interaction). Common structures are found in the tumor-associated and leukocyte-associated antigens. Metastatic potential of tumor cells as well as transendothelial migration of leukocytes was suppressed by agents, or combinations of agents of the groups: (a) carbohydrate antigens; (b) antibodies directed to those antigens; (c) oligosaccharide components of those antigens; (d) conjugates of the antigens or oligosaccharides; and (e) mimetics of the antigens or oligosaccharides. Disclosed are oligosaccharides and derivatives thereof which inhibit cell adhesion and aggregation mediated by P-selectin (GMP-140) and E-selectin (ELAM-1). Effective agents for those purposes include hybrid sugars comprising multiple epitopes, such as Lex/SLex, combination of individual sugars that comprise a hybrid sugar, which may be presented on liposomes, and antibodies or combinations of antibodies directed thereto.