Tumor-associated CD75s gangliosides and CD75s-bearing glycoproteins with Neu5Acα2-6Galβ1-4GlcNAc-residues are receptors for the anticancer drug rViscumin
2004
SPECIFIC AIMSThe sialic acid specific ribosome-inactivating protein (RIP) rViscumin is currently under clinical development as an anticancer drug. This study was designed to characterize the fine specificity of rViscumin toward gangliosides, to identify its receptor gangliosides on gastrointestinal tumors, and to investigate whether the identified receptor gangliosides show an enhanced expression in tumor tissues compared with unaffected tissues. To further characterize the distinct specificities of rViscumin and ricin, an rViscumin homologous but galactoside-specific RIP, solid-phase binding assays were performed with reference glycoproteins varying in type and degree of sialylation.PRINCIPAL FINDINGS1. rViscumin is a lectin with CD75s-specific binding characteristicsCD75s is a carbohydrate epitope with the sialylated lactosaminyl group Neu5Acα2-6Galβ1-4GlcNAc-R. Comparative TLC binding assays with CD75s-specific monoclonal antibodies (mAbs) and a CD75s-specific polyclonal antibody revealed rViscumin to ...
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