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Updated: Feb 15, 2026

Generation of Monoclonal Antibodies Against Natural Products
Published on: April 6, 2019
HMMC-1: a humanized monoclonal antibody with therapeutic potential against Müllerian duct-related carcinomas
Shiro Nozawa1, Daisuke Aoki, Katsumi Tsukazaki
1Department of Obstetrics and Gynecology and Division of Diagnostic Pathology, School of Medicine, Keio University, Tokyo, Japan. shiron@sc.itc.keio.ac.jp
Purpose:
The purpose of this research was to generate a human monoclonal antibody specific to gynecological cancers and to evaluate such an antibody as therapy for gynecological cancers.
Experimental Design:
Transchromosomal KM mice were immunized with the human uterine endometrial cancer cell line SNG-S. Hybridomas were constructed between spleen cells from KM mice and mouse myeloma cells. Reactivity of the antibody was evaluated by immunohistochemistry of pathological specimens of gynecological cancers. Cytotoxicity of HMMC-1 against SNG-S cells was tested by in vitro cytotoxicity assays. The epitope of HMMC-1 was determined by transfection with a panel of glycosyltransferase cDNAs and by inhibition assays with chemically synthesized oligosaccharides.
Results:
HMMC-1 is a human IgM monoclonal antibody that reacts positively with mullerian duct-related carcinomas with positive rates of 54.6% against uterine endometrial adenocarcinoma, 76.9% against uterine cervical adenocarcinoma, and 75.0% against epithelial ovarian cancer. HMMC-1 does not react with normal endometrium at proliferative or secretory phases, normal uterine cervix, or normal and malignant tissue from other organs, whereas it reacts weakly with the epithelium of the gall bladder and the collecting duct of the kidney. HMMC-1 exhibits antigen-dependent and complement-mediated cytotoxicity. Upon cotransfection with cDNAs encoding two glycosyltransferases required for fucosylated extended core 1 O-glycan, mammalian cells express HMMC-1 antigen. Finally, binding of HMMC-1 to SNG-S cells is inhibited by synthetic Fucalpha1-->2Galbeta1-->4GlcNAcbeta1-->3Galbeta1-->3GalNAcalpha1-octyl.
Conclusions:
These results indicate that HMMC-1 specifically recognizes a novel O-glycan structure. The unique specificity and cytotoxicity of HMMC-1 strongly suggest a therapeutic potential of this antibody.
Insights
Researchers developed a human monoclonal antibody, HMMC-1, that targets gynecological cancers. This antibody shows potential for cancer therapy due to its specific reactivity and cell-killing ability.
Area of Science:
- Immunology
- Oncology
- Glycobiology
Background:
- Gynecological cancers pose a significant health challenge.
- Development of targeted therapies is crucial for improving patient outcomes.
Purpose of the Study:
- To generate a human monoclonal antibody specific to gynecological cancers.
- To evaluate the therapeutic potential of this antibody for gynecological cancer treatment.
Main Methods:
- Immunization of mice with a human uterine endometrial cancer cell line.
- Hybridoma construction and antibody characterization.
- Immunohistochemistry, in vitro cytotoxicity assays, and epitope mapping.
Main Results:
- The human IgM monoclonal antibody HMMC-1 demonstrated reactivity with various gynecological carcinomas.
- HMMC-1 exhibited antigen-dependent and complement-mediated cytotoxicity.
- The antibody recognizes a novel O-glycan structure, specifically a fucosylated extended core 1 O-glycan.
Conclusions:
- HMMC-1 specifically recognizes a novel O-glycan structure found on gynecological cancers.
- The antibody's unique specificity and cytotoxic properties suggest significant therapeutic potential.
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