Coxsackievirus B3 is an oncolytic virus with immunostimulatory properties that is active against lung adenocarcinoma

Shohei Miyamoto, Hiroyuki Inoue, Takafumi Nakamura, Meiko Yamada, Chika Sakamoto, Yasuo Urata, Toshihiko Okazaki, Tomotoshi Marumoto, Atsushi Takahashi, Koichi Takayama, Yoichi Nakanishi, Hiroyuki Shimizu, Kenzaburo Tani

研究成果: ジャーナルへの寄稿記事

91 引用 (Scopus)

抄録

Although oncolytic virotherapy is a promising anticancer therapy, antitumor efficacy is hampered by low tumor selectivity. To identify a potent and selective oncolytic virotherapy, we carried out large-scale two-step screening of 28 enteroviral strains and found that coxsackievirus B3 (CVB3) possessed specific oncolytic activity against nine human non-small cell lung cancer (NSCLC) cell lines. CVB3-mediated cytotoxicity was positively correlated with the expression of the viral receptors, coxsackievirus and adenovirus receptor, and decayaccelerating factor, on NSCLC cells. In vitro assays revealed that the CVB3 induced apoptosis and phosphoinositide 3-kinase/Akt and mitogen-activated protein (MAP)/extracellular signal-regulated (ERK) kinase (MEK) survival signaling pathways, leading to cytotoxicity and regulation of CVB3 replication. Intratumoral injections of CVB3 elicited remarkable regression of preestablished NSCLC tumors in vivo. Furthermore, administrations of CVB3 into xenografts on the right flank resulted in significantly durable regression of uninjected xenografts on the left flank, where replication-competent CVB3 was detected. All treatments with CVB3 were well tolerated without treatment-related deaths. In addition, after CVB3 infection, NSCLC cells expressed abundant cell surface calreticulin and secreted ATP as well as translocated extranuclear high-mobility group box 1, which are required for immunogenic cell death. Moreover, intratumoral CVB3 administration markedly recruited natural killer cells and granulocytes, both of which contributed to the antitumor effects as shown by depletion assays, macrophages, and mature dendritic cells into tumor tissues. Together, our findings suggest that CVB3 is a potent and well-tolerated oncolytic agent with immunostimulatory properties active against both localized and metastatic NSCLC.

元の言語英語
ページ(範囲)2609-2621
ページ数13
ジャーナルCancer Research
72
発行部数10
DOI
出版物ステータス出版済み - 5 15 2012

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Oncolytic Viruses
Enterovirus
Non-Small Cell Lung Carcinoma
Oncolytic Virotherapy
Heterografts
Adenocarcinoma of lung
Coxsackievirus Infections
Calreticulin
Neoplasms
1-Phosphatidylinositol 4-Kinase
Mitogen-Activated Protein Kinase Kinases
Extracellular Signal-Regulated MAP Kinases
Mitogens
Granulocytes
Natural Killer Cells
Dendritic Cells
Cell Death

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

Miyamoto, S., Inoue, H., Nakamura, T., Yamada, M., Sakamoto, C., Urata, Y., ... Tani, K. (2012). Coxsackievirus B3 is an oncolytic virus with immunostimulatory properties that is active against lung adenocarcinoma. Cancer Research, 72(10), 2609-2621. https://doi.org/10.1158/0008-5472.CAN-11-3185

Coxsackievirus B3 is an oncolytic virus with immunostimulatory properties that is active against lung adenocarcinoma. / Miyamoto, Shohei; Inoue, Hiroyuki; Nakamura, Takafumi; Yamada, Meiko; Sakamoto, Chika; Urata, Yasuo; Okazaki, Toshihiko; Marumoto, Tomotoshi; Takahashi, Atsushi; Takayama, Koichi; Nakanishi, Yoichi; Shimizu, Hiroyuki; Tani, Kenzaburo.

:: Cancer Research, 巻 72, 番号 10, 15.05.2012, p. 2609-2621.

研究成果: ジャーナルへの寄稿記事

Miyamoto, S, Inoue, H, Nakamura, T, Yamada, M, Sakamoto, C, Urata, Y, Okazaki, T, Marumoto, T, Takahashi, A, Takayama, K, Nakanishi, Y, Shimizu, H & Tani, K 2012, 'Coxsackievirus B3 is an oncolytic virus with immunostimulatory properties that is active against lung adenocarcinoma', Cancer Research, 巻. 72, 番号 10, pp. 2609-2621. https://doi.org/10.1158/0008-5472.CAN-11-3185
Miyamoto, Shohei ; Inoue, Hiroyuki ; Nakamura, Takafumi ; Yamada, Meiko ; Sakamoto, Chika ; Urata, Yasuo ; Okazaki, Toshihiko ; Marumoto, Tomotoshi ; Takahashi, Atsushi ; Takayama, Koichi ; Nakanishi, Yoichi ; Shimizu, Hiroyuki ; Tani, Kenzaburo. / Coxsackievirus B3 is an oncolytic virus with immunostimulatory properties that is active against lung adenocarcinoma. :: Cancer Research. 2012 ; 巻 72, 番号 10. pp. 2609-2621.
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abstract = "Although oncolytic virotherapy is a promising anticancer therapy, antitumor efficacy is hampered by low tumor selectivity. To identify a potent and selective oncolytic virotherapy, we carried out large-scale two-step screening of 28 enteroviral strains and found that coxsackievirus B3 (CVB3) possessed specific oncolytic activity against nine human non-small cell lung cancer (NSCLC) cell lines. CVB3-mediated cytotoxicity was positively correlated with the expression of the viral receptors, coxsackievirus and adenovirus receptor, and decayaccelerating factor, on NSCLC cells. In vitro assays revealed that the CVB3 induced apoptosis and phosphoinositide 3-kinase/Akt and mitogen-activated protein (MAP)/extracellular signal-regulated (ERK) kinase (MEK) survival signaling pathways, leading to cytotoxicity and regulation of CVB3 replication. Intratumoral injections of CVB3 elicited remarkable regression of preestablished NSCLC tumors in vivo. Furthermore, administrations of CVB3 into xenografts on the right flank resulted in significantly durable regression of uninjected xenografts on the left flank, where replication-competent CVB3 was detected. All treatments with CVB3 were well tolerated without treatment-related deaths. In addition, after CVB3 infection, NSCLC cells expressed abundant cell surface calreticulin and secreted ATP as well as translocated extranuclear high-mobility group box 1, which are required for immunogenic cell death. Moreover, intratumoral CVB3 administration markedly recruited natural killer cells and granulocytes, both of which contributed to the antitumor effects as shown by depletion assays, macrophages, and mature dendritic cells into tumor tissues. Together, our findings suggest that CVB3 is a potent and well-tolerated oncolytic agent with immunostimulatory properties active against both localized and metastatic NSCLC.",
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AU - Miyamoto, Shohei

AU - Inoue, Hiroyuki

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AU - Sakamoto, Chika

AU - Urata, Yasuo

AU - Okazaki, Toshihiko

AU - Marumoto, Tomotoshi

AU - Takahashi, Atsushi

AU - Takayama, Koichi

AU - Nakanishi, Yoichi

AU - Shimizu, Hiroyuki

AU - Tani, Kenzaburo

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