Anti‑EpCAM monoclonal antibody exerts antitumor activity against oral squamous cell carcinomas
| Autor: | Junko Takei, Takuro Nakamura, Masato Sano, Tomokazu Ohishi, Hideki Hosono, Hiroyuki Harada, Yusuke Sayama, Mika K. Kaneko, Teizo Asano, Manabu Kawada, Miyuki Yanaka, Yukinari Kato |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research medicine.drug_class Cell Apoptosis CHO Cells Monoclonal antibody Flow cytometry Mice 03 medical and health sciences chemistry.chemical_compound Antineoplastic Agents Immunological Cricetulus 0302 clinical medicine Cell Line Tumor medicine Animals Humans antitumor activity Cell adhesion Antibody-dependent cell-mediated cytotoxicity medicine.diagnostic_test Squamous Cell Carcinoma of Head and Neck Chemistry Antibody-Dependent Cell Cytotoxicity Antibodies Monoclonal Epithelial cell adhesion molecule Articles General Medicine oral cancer Cell cycle Epithelial Cell Adhesion Molecule Xenograft Model Antitumor Assays stomatognathic diseases 030104 developmental biology medicine.anatomical_structure Oncology monoclonal antibody Cell culture EpCAM 030220 oncology & carcinogenesis Cancer research Female Mouth Neoplasms ADCC CDC |
| Zdroj: | Oncology Reports |
| ISSN: | 1791-2431 1021-335X |
| Popis: | The epithelial cell adhesion molecule (EpCAM) is a calcium‑independent, homophilic, intercellular adhesion factor classified as a transmembrane glycoprotein. In addition to cell adhesion, EpCAM also contributes to cell signaling, differentiation, proliferation, and migration. EpCAM is an essential factor in the carcinogenesis of numerous human cancers. In the present study, we developed and validated an anti‑EpCAM monoclonal antibody (mAb), EpMab‑16 (IgG2a, kappa), by immunizing mice with EpCAM‑overexpressing CHO‑K1 cells. EpMab‑16 specifically reacted with endogenous EpCAM in oral squamous cell carcinoma (OSCC) cell lines in flow cytometry and Western blot analyses. It exhibited a plasma membrane‑like stain pattern in OSCC tissues upon immunohistochemical analysis. The KD for EpMab‑16 in SAS and HSC‑2 OSCC cells were assessed via flow cytometry at 1.1x10‑8 and 1.9x10‑8 M, respectively, suggesting moderate binding affinity of EpMab‑16 for EpCAM. We then assessed whether the EpMab‑16 induced antibody‑dependent cellular cytotoxicity (ADCC) and complement‑dependent cytotoxicity (CDC) against OSCC cell lines, and antitumor capacity in a murine xenograft model. In vitro experiments revealed strong ADCC and CDC inducement against OSCC cells treated with EpMab‑16. In vivo experiments on OSCC xenografts revealed that EpMab‑16 treatment significantly reduced tumor growth compared with the control mouse IgG. These data indicated that EpMab‑16 could be a promising treatment option for EpCAM‑expressing OSCCs. |
| Databáze: | OpenAIRE |
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