Humanized anti-CD271 monoclonal antibody exerts an anti-tumor effect by depleting cancer stem cells
| Autor: | Yukinori Asada, Shinkichi Morita, Kazunori Yamaguchi, Kazuo Sugamura, Rie Shibuya, Mai Mochizuki, Kouichi Wada, Kennichi Satoh, Kazuto Matsuura, Takayuki Imai, Yukio Katori, Mao Nakamura, Keiichi Tamai, Tomoko Yamazaki |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research Lung Neoplasms medicine.drug_class Apoptosis Nerve Tissue Proteins Mice SCID Receptors Nerve Growth Factor Monoclonal antibody Antibodies Monoclonal Humanized 03 medical and health sciences Mice 0302 clinical medicine Cancer stem cell Mice Inbred NOD medicine Tumor Cells Cultured Animals Humans Receptor Cytotoxicity Melanoma Cell Proliferation Antibody-dependent cell-mediated cytotoxicity Mice Inbred BALB C Hypopharyngeal Neoplasms business.industry Antibody-Dependent Cell Cytotoxicity Hypopharyngeal cancer medicine.disease Xenograft Model Antitumor Assays 030104 developmental biology Oncology Cell culture 030220 oncology & carcinogenesis Cancer research Neoplastic Stem Cells Female business |
| Zdroj: | Cancer letters. 461 |
| ISSN: | 1872-7980 |
| Popis: | CD271, known as a neurotrophin receptor, is expressed in various cancers such as hypopharyngeal cancer (HPC) and melanoma. We recently reported that CD271 is a cancer-stem-cell biomarker of HPC, and that its expression is essential for cancer-cell proliferation and is correlated with a poor prognosis in this disease. Here, to develop a therapeutic antibody to CD271, we established a humanized anti-CD271 monoclonal antibody (hCD271 mA b). hCD271 mA b bound to the cysteine-rich domain 1 (CRD1) of human CD271 with high affinity (KD = 1.697 × 10−9 M). In vitro, hCD271 mA b exerted antibody-dependent cell-mediated cytotoxicity (ADCC) activity against SP2/0-CD271 (human CD271-transduced mouse cell line). Treatment with hCD271 mA b also exerted anti-tumor activity in graft models of three cell lines (HPCM2 (patient-derived xenograft cell line of hypopharyngeal cancer), MeWo-Luc (melanoma cell line), and SP2/0-CD271) in mice, resulting in smaller tumors compared to controls and reduced numbers of CD271-positive cells. Collectively, these data suggest that an antibody targeting CD271 is a promising therapeutic strategy. |
| Databáze: | OpenAIRE |
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