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Development of a complete human IgG monoclonal antibody to transferrin receptor 1 targeted for adult T-cell leukemia/lymphoma
http://hdl.handle.net/10458/0002000455
http://hdl.handle.net/10458/000200045578b8e7d1-953b-4fa3-aceb-60b7e5efb28f
| Item type | 学術雑誌論文 / Journal Article(1) | |||||||||||||
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| 公開日 | 2024-01-26 | |||||||||||||
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| タイトル | Development of a complete human IgG monoclonal antibody to transferrin receptor 1 targeted for adult T-cell leukemia/lymphoma | |||||||||||||
| 言語 | en | |||||||||||||
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| 言語 | eng | |||||||||||||
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| 資源タイプ | journal article | |||||||||||||
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| 著者 |
下崎, 俊介
× 下崎, 俊介× Nakahata, Shingo× Ichikawa, Tomonaga× 北中, 明× 亀田, 拓郎× 日髙, 智徳× 久冨木, 庸子× Kurosawa, Gene× Zhang, Lilin× Sudo, Yukio× 下田, 和哉
WEKO
7997
× 森下, 和広 |
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| 抄録 | ||||||||||||||
| 内容記述タイプ | Abstract | |||||||||||||
| 内容記述 | Iron is an essential nutrient for normal cell growth, and reprogramming of iron metabolism is essential to tumor cell survival and progression. HTLV-1-associated adult T-cell leukemia/lymphoma (ATLL) has no effective therapy and high levels of cell surface transferrin receptor 1 (TFR1) expression have been reported in ATLL by us and other groups. In this study, to develop a novel molecular-targeted therapy against TFR1 to modulate iron metabolism, we initially determined the expression pattern of several iron-related genes along with TFR1 and found that ATLL cells presented characteristic of an iron-deficiency state such as high expression of iron-regulatory protein 2 (IRP2) and low expression of its E3 ubiquitin-ligase, FBXL5. Therefore, we developed human IgG monoclonal antibodies to human TFR1 using a phage display method (ICOS method) to block the incorporation of the transferrin (TF)-iron complex into ATLL cells for inhibiting cell growth. One of the mAbs, JST-TFR09, presented its greater affinity to TFR1 on ATLL cells in flow cytometry (FCM) analysis than those of commercially available anti-TFR1 antibodies and identified high expression of TFR1 in most of the acute-type ATLL cells. Moreover, JST-TFR09 could interfere with binding between TFR1 and TF, which resulted in effective blockade of TFR1 internalization and induction of cell apoptosis by the treatment of ATLL cells with JST-TFR09. JST-TFR09 showed dual activities through direct cell cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC), and the treatment of JST-TFR09 significantly suppressed cell growth of ATLL cells with induction of apoptosis in in vitro and in vivo experiments. Thus, JST-TFR09 described here may become a promising therapeutic antibody for the treatment of ATLL. | |||||||||||||
| 言語 | en | |||||||||||||
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| 内容記述タイプ | Other | |||||||||||||
| 内容記述 | Citation: Shimosaki S, Nakahata S, Ichikawa T, Kitanaka A, Kameda T, Hidaka T, Kubuki Y, Kurosawa G, Zhang L, Sudo Y, Shimoda K, Morishita K. Development of a complete human IgG monoclonal antibody to transferrin receptor 1 targeted for adult T-cell leukemia/lymphoma. Biochem Biophys Res Commun. 2017 Mar 25;485(1):144-151. doi: 10.1016/j.bbrc.2017.02.039. Epub 2017 Feb 8. Erratum in: Biochem Biophys Res Commun. 2020 Sep 17;530(2):486. PMID: 28189691. |
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| 言語 | en | |||||||||||||
| 書誌情報 |
en : Biochemical and Biophysical Research Communications 巻 485, 号 1, p. 144-151, 発行日 2017-03-25 |
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| 出版者 | Elsevier | |||||||||||||
| 言語 | en | |||||||||||||
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| 収録物識別子タイプ | ISSN | |||||||||||||
| 収録物識別子 | 0006291X | |||||||||||||
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| 関連タイプ | isVersionOf | |||||||||||||
| 識別子タイプ | DOI | |||||||||||||
| 関連識別子 | https://doi.org/10.1016/j.bbrc.2017.02.039 | |||||||||||||
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| 出版タイプ | NA | |||||||||||||
