Abstract | BACKGROUND: METHODS: To determine the expression of Nectin-2 in cancer tissues and cancer cell lines, we performed gene expression profile analysis, immunohistochemistry studies, and flow cytometry analysis. We also investigated the potential of this molecule as a target for antibody therapeutics to treat cancers by generating and characterizing an anti-Nectin-2 rabbit polyclonal antibody (poAb) and 256 fully human anti-Nectin-2 monoclonal antibodies (mAbs). In addition, we tested anti-Nectin-2 mAbs in several in vivo tumor growth inhibition models to investigate the primary mechanisms of action of the mAbs. RESULTS: In the present study, we found that Nectin-2 was over-expressed in clinical breast and ovarian cancer tissues by using gene expression profile analysis and immunohistochemistry studies. Nectin-2 was over-expressed in various cancer cell lines as well. Furthermore, the polyclonal antibody specific to Nectin-2 suppressed the in vitro proliferation of OV-90 ovarian cancer cells, which express endogenous Nectin-2 on the cell surface. The anti-Nectin-2 mAbs we generated were classified into 7 epitope bins. The anti-Nectin-2 mAbs demonstrated antibody-dependent cellular cytotoxicity (ADCC) and epitope bin-dependent features such as the inhibition of Nectin-2-Nectin-2 interaction, Nectin-2-Nectin-3 interaction, and in vitro cancer cell proliferation. A representative anti-Nectin-2 mAb in epitope bin VII, Y-443, showed anti- tumor effects against OV-90 cells and MDA-MB-231 breast cancer cells in mouse therapeutic models, and its main mechanism of action appeared to be ADCC. CONCLUSIONS:
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Authors | Tsutomu Oshima, Shuji Sato, Junichi Kato, Yuki Ito, Takahiro Watanabe, Isamu Tsuji, Akira Hori, Tomofumi Kurokawa, Toshio Kokubo |
Journal | Molecular cancer
(Mol Cancer)
Vol. 12
Pg. 60
(Jun 12 2013)
ISSN: 1476-4598 [Electronic] England |
PMID | 23758976
(Publication Type: Journal Article)
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Chemical References |
- Antibodies, Monoclonal, Humanized
- Antineoplastic Agents
- Cell Adhesion Molecules
- Epitopes
- NECTIN3 protein, human
- Nectin3 protein, mouse
- Nectins
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Topics |
- Animals
- Antibodies, Monoclonal, Humanized
(administration & dosage, immunology, pharmacology)
- Antibody-Dependent Cell Cytotoxicity
(drug effects, immunology)
- Antineoplastic Agents
(administration & dosage, pharmacology)
- Breast Neoplasms
(genetics, immunology, metabolism)
- Cell Adhesion Molecules
(genetics, immunology, metabolism)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Disease Models, Animal
- Epitopes
(immunology)
- Female
- Gene Expression
- Humans
- Mice
- Nectins
- Ovarian Neoplasms
(genetics, immunology, metabolism)
- Protein Binding
(drug effects)
- Xenograft Model Antitumor Assays
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