論文 - 詳細
| RRC ID | 76959 |
|---|---|
| 著者 | Morita S, Mochizuki M, Wada K, Shibuya R, Nakamura M, Yamaguchi K, Yamazaki T, Imai T, Asada Y, Matsuura K, Sugamura K, Katori Y, Satoh K, Tamai K. |
| タイトル | Humanized anti-CD271 monoclonal antibody exerts an anti-tumor effect by depleting cancer stem cells. |
| ジャーナル | Cancer Lett |
| Abstract |
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. |
| 巻・号 | 461 |
| ページ | 144-152 |
| 公開日 | 2019-10-1 |
| DOI | 10.1016/j.canlet.2019.07.011 |
| PII | S0304-3835(19)30407-0 |
| PMID | 31325530 |
| MeSH | Animals Antibodies, Monoclonal, Humanized / immunology Antibodies, Monoclonal, Humanized / pharmacology* Antibody-Dependent Cell Cytotoxicity* Apoptosis Cell Proliferation Female Humans Hypopharyngeal Neoplasms / drug therapy* Hypopharyngeal Neoplasms / immunology Hypopharyngeal Neoplasms / metabolism Hypopharyngeal Neoplasms / pathology Lung Neoplasms / drug therapy* Lung Neoplasms / immunology Lung Neoplasms / metabolism Lung Neoplasms / pathology Melanoma / drug therapy* Melanoma / immunology Melanoma / metabolism Melanoma / pathology Mice Mice, Inbred BALB C Mice, Inbred NOD Mice, SCID Neoplastic Stem Cells / drug effects* Neoplastic Stem Cells / immunology Neoplastic Stem Cells / metabolism Neoplastic Stem Cells / pathology Nerve Tissue Proteins / immunology* Receptors, Nerve Growth Factor / immunology* Tumor Cells, Cultured Xenograft Model Antitumor Assays |
| IF | 7.36 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | Genome Network Project Human cDNA Clone IRAK090O06 (HGY036342) pEF-BOS-anti human CD271-#16 (RDB20193) |