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Updated: May 10, 2026

In Vivo Immunofluorescence Localization for Assessment of Therapeutic and Diagnostic Antibody Biodistribution in Cancer Research
Published on: September 16, 2019
Nectin-2 is a potential target for antibody therapy of breast and ovarian cancers
Tsutomu Oshima1, Shuji Sato, Junichi Kato
1Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraokahigashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan. tomofumi.kurokawa@takeda.com
Background:
Nectin-2 is a Ca(2+)-independent cell-cell adhesion molecule that is one of the plasma membrane components of adherens junctions. However, little has been reported about the involvement of Nectin-2 in cancer.
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:
We observed the over-expression of Nectin-2 in breast and ovarian cancers and anti-tumor activity of anti-Nectin-2 mAbs via strong ADCC. These findings suggest that Nectin-2 is a potential target for antibody therapy against breast and ovarian cancers.
Insights
Nectin-2 is over-expressed in breast and ovarian cancers. Anti-Nectin-2 monoclonal antibodies (mAbs) show anti-tumor effects, suggesting Nectin-2 is a promising target for antibody therapeutics.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Nectin-2 is a Ca(2+)-independent cell-cell adhesion molecule.
- Its role in cancer, particularly breast and ovarian cancers, is largely unexplored.
Purpose of the Study:
- To investigate Nectin-2 expression in cancer tissues and cell lines.
- To evaluate anti-Nectin-2 antibodies as potential cancer therapeutics.
Main Methods:
- Gene expression profiling, immunohistochemistry, and flow cytometry were used to assess Nectin-2 expression.
- Rabbit polyclonal and human monoclonal antibodies (mAbs) against Nectin-2 were generated and characterized.
- In vitro and in vivo models were employed to test the therapeutic potential of anti-Nectin-2 mAbs.
Main Results:
- Nectin-2 was found to be over-expressed in clinical breast and ovarian cancer tissues and cell lines.
- Anti-Nectin-2 antibodies inhibited cancer cell proliferation in vitro.
- Anti-Nectin-2 mAbs exhibited antibody-dependent cellular cytotoxicity (ADCC) and demonstrated anti-tumor effects in vivo, with mechanisms including inhibition of Nectin-2 interactions.
Conclusions:
- Nectin-2 is over-expressed in breast and ovarian cancers.
- Anti-Nectin-2 monoclonal antibodies show significant anti-tumor activity, primarily through ADCC.
- Nectin-2 represents a potential therapeutic target for antibody-based treatments in breast and ovarian cancers.
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