COMPOSITIONS AND METHODS FOR ENDOTHELIAL BINDING

摘要

Novel methods and compositions are provided for modulating homing of leukocytes, particularly lymphocytes, where the compounds are cross-reactive with or contain Neu5Ac2-3Gal beta 1-x[Fuc alpha 1-y]GlcNAc, where one of x and y is 3 and the other is 4. These compounds may be administered to a host associated with inflammation, to avoid the deleterious effects of leukocyte infiltration and for directing molecules to such sites. In addition, methods and compositions are disclosed for the inhibition of cancer metastases mediated by endothelial adhesion molecules. The present invention discloses that sialyl-Le and di-sialyl-Le, which are expressed at the surface of cancer cells, function as a binding partner for selectins, such as ELAM-1, which are expressed at the surface of endothelial cells. The present invention also discloses that selectins, such as ELAM-1, LECAM-1 and GMP-140, bind a carbohydrate domain common to both sialyl-Le and sialyl-Le. Antibodies, saccharides, glycoconjugates, enzymes, enzyme inhibitors and other molecules may be used in the methods of the present invention to inhibit the binding of malignant cells to endothelial cells for a variety of purposes in vivo and in vitro.