HMMC-1: A Humanized Monoclonal Antibody With Therapeutic Potential Against Müllerian Duct-Related Carcinomas

摘要: Purpose: The purpose of this research was to generate a human monoclonal antibody specific gynecological cancers and evaluate such an as therapy for cancers. Experimental Design: Transchromosomal KM mice were immunized with the uterine endometrial cancer cell line SNG-S. Hybridomas constructed between spleen cells from mouse myeloma cells. Reactivity evaluated by immunohistochemistry pathological specimens Cytotoxicity HMMC-1 against SNG-S tested in vitro cytotoxicity assays. epitope determined transfection panel glycosyltransferase cDNAs inhibition assays chemically synthesized oligosaccharides. Results: is IgM that reacts positively mullerian duct-related carcinomas positive rates 54.6% adenocarcinoma, 76.9% cervical 75.0% epithelial ovarian cancer. does not react normal endometrium at proliferative or secretory phases, cervix, malignant tissue other organs, whereas it weakly epithelium gall bladder collecting duct kidney. exhibits antigen-dependent complement-mediated cytotoxicity. Upon cotransfection encoding two glycosyltransferases required fucosylated extended core 1 O-glycan, mammalian express antigen. Finally, binding inhibited synthetic Fucα1→2Galβ1→4GlcNAcβ1→3Galβ1→3GalNAcα1-octyl. Conclusions: These results indicate specifically recognizes novel O-glycan structure. unique specificity strongly suggest therapeutic potential antibody.