ID | 60900 |
フルテキストURL | |
著者 |
Mochizuki, Yusuke
Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Tazawa, Hiroshi
Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Demiya, Koji
Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kure, Miho
Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kondo, Hiroya
Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Komatsubara, Tadashi
Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Sugiu, Kazuhisa
Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Hasei, Joe
Sports Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
Yoshida, Aki
Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kunisada, Toshiyuki
Medical Materials for Musculoskeletal Reconstruction, Okayama University Graduate School of Medicine
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Urata, Yasuo
Oncolys BioPharma, Inc,
Kagawa, Shunsuke
Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Ozaki, Toshifumi
Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Fujiwara, Toshiyoshi
Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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抄録 | Immune checkpoint inhibitors including anti-programmed cell death 1 (PD-1) antibody have recently improved clinical outcome in certain cancer patients; however, osteosarcoma (OS) patients are refractory to PD-1 blockade. Oncolytic virotherapy has emerged as novel immunogenic therapy to augment antitumor immune response. We developed a telomerase-specific replication-competent oncolytic adenovirus OBP-502 that induces lytic cell death via binding to integrins. In this study, we assessed the combined effect of PD-1 blockade and OBP-502 in OS cells. The expression of coxsackie and adenovirus receptor (CAR), integrins αvβ3 and αvβ5, and programmed cell death ligand 1 (PD-L1) was analyzed in two murine OS cells (K7M2, NHOS). The cytopathic activity of OBP-502 in both cells was analyzed using the XTT assay. OBP-502-induced immunogenic cell death was assessed by analyzing the level of extracellular ATP and high-mobility group box protein B1 (HMGB1). Subcutaneous tumor models for K7M2 and NHOS cells were used to evaluate the antitumor effect and number of tumor-infiltrating CD8+ cells in combination therapy. K7M2 and NHOS cells showed high expression of integrins αvβ3 and αvβ5, but not CAR. OBP-502 significantly suppressed the viability of both cells, in which PD-L1 expression and the release of ATP and HMGB1 were significantly increased. Intratumoral injection of OBP-502 significantly augmented the efficacy of PD-1 blockade on subcutaneous K2M2 and NHOS tumor models via enhancement of tumor-infiltrating CD8+ T cells. Our results suggest that telomerase-specific oncolytic virotherapy is a promising antitumor strategy to promote the efficacy of PD-1 blockade in OS.
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キーワード | Oncolytic adenovirus
hTERT
Immunogenic cell death
ATP
CD8
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備考 | This is a post-peer-review, pre-copyedit version of an article published in Cancer Immunology, Immunotherapy. The final authenticated version is available online at: http://dx.doi.org/10.1007/s00262-020-02774-7.
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発行日 | 2020-11-05
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出版物タイトル |
Cancer Immunology, Immunotherapy
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巻 | 70巻
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出版者 | Springer
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開始ページ | 1405
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終了ページ | 1417
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ISSN | 0340-7004
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NCID | AA00598499
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資料タイプ |
学術雑誌論文
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言語 |
英語
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OAI-PMH Set |
岡山大学
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論文のバージョン | author
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PubMed ID | |
DOI | |
Web of Science KeyUT | |
関連URL | isVersionOf https://doi.org/10.1007/s00262-020-02774-7
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助成機関名 |
文部科学省
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助成番号 | 16H05416
19H03731
25293323
16K10862
15K10446
18K15242
16K10596
19K16835
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