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In vivo validation of the switch antibody concept: SPECT/CT imaging of the anti-CD137 switch antibody Sta-MB shows high uptake in tumors but low uptake in normal organs in human CD137 knock-in mice.
https://repo.qst.go.jp/records/86561
https://repo.qst.go.jp/records/865617b48d70c-2f62-49ea-b41d-29cf20f82a99
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2022-07-12 | |||||
| タイトル | ||||||
| タイトル | In vivo validation of the switch antibody concept: SPECT/CT imaging of the anti-CD137 switch antibody Sta-MB shows high uptake in tumors but low uptake in normal organs in human CD137 knock-in mice. | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Sugyo, Aya
× Sugyo, Aya× B Tsuji, Atsushi× Sudo, Hitomi× Narita, Yoshinori× Taniguchi, Kenji× Nemoto, Takayuki× Isomura, Fumihisa× Awaya, Norihiro× Mika, Kamata-Sakurai× Higashi, Tatsuya× Aya, Sugyo× Atsushi, Tsuji× Hitomi, Sudo× Tatsuya, Higashi |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | CD137 is an attractive target for cancer immunotherapy, but its expression in normal tissues induces some adverse effects in patients receiving CD137-targeted therapy. To overcome this issue, we developed a switch antibody, STA551, that binds to CD137 only under high ATP concentrations around cells. This study quantified biodistribution of murine switch antibodies in human CD137 knock-in mice to show the viability of the switch antibody concept in vivo. We utilized four antibodies: Sta-MB, Ure-MB, Sta-mIgG, and KLH-MB. Sta-MB is a switch antibody having the variable region of STA551. The MB is a murine Fc highly binding to murine Fcγ receptor II. Ure-MB has a variable region mimicking the clinically available anti-CD137 agonist antibody urelumab, binding to CD137 regardless of ATP concentration. Sta-mIgG has the same variable region as Sta-MB but has the standard murine constant region. KLH-MB binds to keyhole limpet hemocyanin. The four antibodies were radiolabeled with In-111, SPECT/CT imaging was conducted in human CD137 knock-in mice, and the uptake in regions of interest was quantified. In-labeled Sta-MB and Sta-mIgG showed high uptake in tumors but low uptake in the lymph nodes and spleen in human CD137 knock-in mice. On the other hand, Ure-MB highly accumulated not only in tumors but also in the lymph nodes and spleen. KLH-MB showed low uptake in the tumors, lymph nodes, and spleen. The present study provides evidence that the switch antibody concept works in vivo. Our findings encourage further clinical imaging studies to evaluate the biodistribution of STA551 in patients. | |||||
| 書誌情報 |
Translational oncology 巻 23, p. 101481, 発行日 2022-07 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 1936-5233 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 35820360 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1016/j.tranon.2022.101481 | |||||
