Treatment of Human Glioblastoma with a Live Attenuated Zika Virus Vaccine Candidate

ABSTRACT Glioblastoma (GBM) is the deadliest type of brain tumor, and glioma stem cells (GSCs) contribute to tumor recurrence and therapeutic resistance. Thus, an oncolytic virus targeting GSCs may be useful for improving GBM treatment. Because Zika virus (ZIKV) has an oncolytic tropism for infectin...

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Autores principales:	Qi Chen, Jin Wu, Qing Ye, Feng Ma, Qian Zhu, Yan Wu, Chao Shan, Xuping Xie, Dapei Li, Xiaoyan Zhan, Chunfeng Li, Xiao-Feng Li, Xiaoling Qin, Tongyan Zhao, Haitao Wu, Pei-Yong Shi, Jianghong Man, Cheng-Feng Qin
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Zika virus anticancer therapy glioblastoma vaccine Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/07ea5ab958ca49449dd9b7a5bae0a153
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spelling	oai:doaj.org-article:07ea5ab958ca49449dd9b7a5bae0a1532021-11-15T15:58:20ZTreatment of Human Glioblastoma with a Live Attenuated Zika Virus Vaccine Candidate10.1128/mBio.01683-182150-7511https://doaj.org/article/07ea5ab958ca49449dd9b7a5bae0a1532018-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01683-18https://doaj.org/toc/2150-7511ABSTRACT Glioblastoma (GBM) is the deadliest type of brain tumor, and glioma stem cells (GSCs) contribute to tumor recurrence and therapeutic resistance. Thus, an oncolytic virus targeting GSCs may be useful for improving GBM treatment. Because Zika virus (ZIKV) has an oncolytic tropism for infecting GSCs, we investigated the safety and efficacy of a live attenuated ZIKV vaccine candidate (ZIKV-LAV) for the treatment of human GBM in a GSC-derived orthotopic model. Intracerebral injection of ZIKV-LAV into mice caused no neurological symptoms or behavioral abnormalities. The neurovirulence of ZIKV-LAV was more attenuated than that of the licensed Japanese encephalitis virus LAV 14-14-2, underlining the superior safety of ZIKV-LAV for potential GBM treatment. Importantly, ZIKV-LAV significantly reduced intracerebral tumor growth and prolonged animal survival by selectively killing GSCs within the tumor. Mechanistically, ZIKV infection elicited antiviral immunity, inflammation, and GSC apoptosis. Together, these results further support the clinical development of ZIKV-LAV for GBM therapy. IMPORTANCE Glioblastoma (GBM), the deadliest type of brain tumor, is currently incurable because of its high recurrence rate after traditional treatments, including surgery to remove the main part of the tumor and radiation and chemotherapy to target residual tumor cells. These treatments fail mainly due to the presence of a cell subpopulation called glioma stem cells (GSCs), which are resistant to radiation and chemotherapy and capable of self-renewal and tumorigenicity. Because Zika virus (ZIKV) has an oncolytic tropism for infecting GSCs, we tested a live attenuated ZIKV vaccine candidate (ZIKV-LAV) for the treatment of human GBM in a human GSC-derived orthotopic model. Our results showed that ZIKV-LAV retained good efficacy against glioblastoma by selectively killing GSCs within the tumor. In addition, ZIKV-LAV exhibited an excellent safety profile upon intracerebral injection into the treated animals. The good balance between the safety of ZIKV-LAV and its efficacy against human GSCs suggests that it is a potential candidate for combination with the current treatment regimen for GBM therapy.Qi ChenJin WuQing YeFeng MaQian ZhuYan WuChao ShanXuping XieDapei LiXiaoyan ZhanChunfeng LiXiao-Feng LiXiaoling QinTongyan ZhaoHaitao WuPei-Yong ShiJianghong ManCheng-Feng QinAmerican Society for MicrobiologyarticleZika virusanticancer therapyglioblastomavaccineMicrobiologyQR1-502ENmBio, Vol 9, Iss 5 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Zika virus anticancer therapy glioblastoma vaccine Microbiology QR1-502
spellingShingle	Zika virus anticancer therapy glioblastoma vaccine Microbiology QR1-502 Qi Chen Jin Wu Qing Ye Feng Ma Qian Zhu Yan Wu Chao Shan Xuping Xie Dapei Li Xiaoyan Zhan Chunfeng Li Xiao-Feng Li Xiaoling Qin Tongyan Zhao Haitao Wu Pei-Yong Shi Jianghong Man Cheng-Feng Qin Treatment of Human Glioblastoma with a Live Attenuated Zika Virus Vaccine Candidate
description	ABSTRACT Glioblastoma (GBM) is the deadliest type of brain tumor, and glioma stem cells (GSCs) contribute to tumor recurrence and therapeutic resistance. Thus, an oncolytic virus targeting GSCs may be useful for improving GBM treatment. Because Zika virus (ZIKV) has an oncolytic tropism for infecting GSCs, we investigated the safety and efficacy of a live attenuated ZIKV vaccine candidate (ZIKV-LAV) for the treatment of human GBM in a GSC-derived orthotopic model. Intracerebral injection of ZIKV-LAV into mice caused no neurological symptoms or behavioral abnormalities. The neurovirulence of ZIKV-LAV was more attenuated than that of the licensed Japanese encephalitis virus LAV 14-14-2, underlining the superior safety of ZIKV-LAV for potential GBM treatment. Importantly, ZIKV-LAV significantly reduced intracerebral tumor growth and prolonged animal survival by selectively killing GSCs within the tumor. Mechanistically, ZIKV infection elicited antiviral immunity, inflammation, and GSC apoptosis. Together, these results further support the clinical development of ZIKV-LAV for GBM therapy. IMPORTANCE Glioblastoma (GBM), the deadliest type of brain tumor, is currently incurable because of its high recurrence rate after traditional treatments, including surgery to remove the main part of the tumor and radiation and chemotherapy to target residual tumor cells. These treatments fail mainly due to the presence of a cell subpopulation called glioma stem cells (GSCs), which are resistant to radiation and chemotherapy and capable of self-renewal and tumorigenicity. Because Zika virus (ZIKV) has an oncolytic tropism for infecting GSCs, we tested a live attenuated ZIKV vaccine candidate (ZIKV-LAV) for the treatment of human GBM in a human GSC-derived orthotopic model. Our results showed that ZIKV-LAV retained good efficacy against glioblastoma by selectively killing GSCs within the tumor. In addition, ZIKV-LAV exhibited an excellent safety profile upon intracerebral injection into the treated animals. The good balance between the safety of ZIKV-LAV and its efficacy against human GSCs suggests that it is a potential candidate for combination with the current treatment regimen for GBM therapy.
format	article
author	Qi Chen Jin Wu Qing Ye Feng Ma Qian Zhu Yan Wu Chao Shan Xuping Xie Dapei Li Xiaoyan Zhan Chunfeng Li Xiao-Feng Li Xiaoling Qin Tongyan Zhao Haitao Wu Pei-Yong Shi Jianghong Man Cheng-Feng Qin
author_facet	Qi Chen Jin Wu Qing Ye Feng Ma Qian Zhu Yan Wu Chao Shan Xuping Xie Dapei Li Xiaoyan Zhan Chunfeng Li Xiao-Feng Li Xiaoling Qin Tongyan Zhao Haitao Wu Pei-Yong Shi Jianghong Man Cheng-Feng Qin
author_sort	Qi Chen
title	Treatment of Human Glioblastoma with a Live Attenuated Zika Virus Vaccine Candidate
title_short	Treatment of Human Glioblastoma with a Live Attenuated Zika Virus Vaccine Candidate
title_full	Treatment of Human Glioblastoma with a Live Attenuated Zika Virus Vaccine Candidate
title_fullStr	Treatment of Human Glioblastoma with a Live Attenuated Zika Virus Vaccine Candidate
title_full_unstemmed	Treatment of Human Glioblastoma with a Live Attenuated Zika Virus Vaccine Candidate
title_sort	treatment of human glioblastoma with a live attenuated zika virus vaccine candidate
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/07ea5ab958ca49449dd9b7a5bae0a153
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Treatment of Human Glioblastoma with a Live Attenuated Zika Virus Vaccine Candidate

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