Treatment of human glioblastoma with a live attenuated Zika virus vaccine candidate

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, Tongyang Zhao, Haitao Wu, Pei-Yong Shi, Jianghong Man, Cheng Feng Qin

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere01683-18
JournalmBio
Volume9
Issue number5
DOIs
StatePublished - Sep 1 2018

Fingerprint

Glioblastoma
Vaccines
Glioma
Stem Cells
Therapeutics
Neoplastic Stem Cells
Safety
Tropism
Zika Virus
Brain Neoplasms
Japanese Encephalitis Virus
Oncolytic Viruses
Radiation
Recurrence
Drug Therapy
Neoplasms
Behavioral Symptoms
Injections
Residual Neoplasm
Antiviral Agents

Keywords

  • Anticancer therapy
  • Glioblastoma
  • Vaccine
  • Zika virus

ASJC Scopus subject areas

  • Microbiology
  • Virology

Cite this

Chen, Q., Wu, J., Ye, Q., Ma, F., Zhu, Q., Wu, Y., ... Qin, C. F. (2018). Treatment of human glioblastoma with a live attenuated Zika virus vaccine candidate. mBio, 9(5), [e01683-18]. https://doi.org/10.1128/mBio.01683-18

Treatment of human glioblastoma with a live attenuated Zika virus vaccine candidate. / Chen, Qi; Wu, Jin; Ye, Qing; Ma, Feng; Zhu, Qian; Wu, Yan; Shan, Chao; Xie, Xuping; Li, Dapei; Zhan, Xiaoyan; Li, Chunfeng; Li, Xiao Feng; Qin, Xiaoling; Zhao, Tongyang; Wu, Haitao; Shi, Pei-Yong; Man, Jianghong; Qin, Cheng Feng.

In: mBio, Vol. 9, No. 5, e01683-18, 01.09.2018.

Research output: Contribution to journalArticle

Chen, Q, Wu, J, Ye, Q, Ma, F, Zhu, Q, Wu, Y, Shan, C, Xie, X, Li, D, Zhan, X, Li, C, Li, XF, Qin, X, Zhao, T, Wu, H, Shi, P-Y, Man, J & Qin, CF 2018, 'Treatment of human glioblastoma with a live attenuated Zika virus vaccine candidate', mBio, vol. 9, no. 5, e01683-18. https://doi.org/10.1128/mBio.01683-18
Chen, Qi ; Wu, Jin ; Ye, Qing ; Ma, Feng ; Zhu, Qian ; Wu, Yan ; Shan, Chao ; Xie, Xuping ; Li, Dapei ; Zhan, Xiaoyan ; Li, Chunfeng ; Li, Xiao Feng ; Qin, Xiaoling ; Zhao, Tongyang ; Wu, Haitao ; Shi, Pei-Yong ; Man, Jianghong ; Qin, Cheng Feng. / Treatment of human glioblastoma with a live attenuated Zika virus vaccine candidate. In: mBio. 2018 ; Vol. 9, No. 5.
@article{c27b0e3c80c04144a9c2807ff5b35f17,
title = "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 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.",
keywords = "Anticancer therapy, Glioblastoma, Vaccine, Zika virus",
author = "Qi Chen and Jin Wu and Qing Ye and Feng Ma and Qian Zhu and Yan Wu and Chao Shan and Xuping Xie and Dapei Li and Xiaoyan Zhan and Chunfeng Li and Li, {Xiao Feng} and Xiaoling Qin and Tongyang Zhao and Haitao Wu and Pei-Yong Shi and Jianghong Man and Qin, {Cheng Feng}",
year = "2018",
month = "9",
day = "1",
doi = "10.1128/mBio.01683-18",
language = "English (US)",
volume = "9",
journal = "mBio",
issn = "2161-2129",
publisher = "American Society for Microbiology",
number = "5",

}

TY - JOUR

T1 - Treatment of human glioblastoma with a live attenuated Zika virus vaccine candidate

AU - Chen, Qi

AU - Wu, Jin

AU - Ye, Qing

AU - Ma, Feng

AU - Zhu, Qian

AU - Wu, Yan

AU - Shan, Chao

AU - Xie, Xuping

AU - Li, Dapei

AU - Zhan, Xiaoyan

AU - Li, Chunfeng

AU - Li, Xiao Feng

AU - Qin, Xiaoling

AU - Zhao, Tongyang

AU - Wu, Haitao

AU - Shi, Pei-Yong

AU - Man, Jianghong

AU - Qin, Cheng Feng

PY - 2018/9/1

Y1 - 2018/9/1

N2 - 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.

AB - 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.

KW - Anticancer therapy

KW - Glioblastoma

KW - Vaccine

KW - Zika virus

UR - http://www.scopus.com/inward/record.url?scp=85055538764&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85055538764&partnerID=8YFLogxK

U2 - 10.1128/mBio.01683-18

DO - 10.1128/mBio.01683-18

M3 - Article

C2 - 30228241

AN - SCOPUS:85055538764

VL - 9

JO - mBio

JF - mBio

SN - 2161-2129

IS - 5

M1 - e01683-18

ER -