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Neural Stem Cells: What Happens When They Go Viral?
Article

Effect of Serial Systemic and Intratumoral Injections of Oncolytic ZIKVBR in Mice Bearing Embryonal CNS Tumors

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Centro de Estudos do Genoma Humano e Células-Tronco, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, Cidade Universitária, São Paulo 05508-090, SP, Brazil
2
Hemotherapy and Cellular Therapy Department, Hospital Israelita Albert Einstein, São Paulo 05652-900, SP, Brazil
*
Authors to whom correspondence should be addressed.
Academic Editors: Sara Salinas and Muriel Coulpier
Viruses 2021, 13(10), 2103; https://doi.org/10.3390/v13102103
Received: 29 July 2021 / Revised: 7 October 2021 / Accepted: 11 October 2021 / Published: 19 October 2021
(This article belongs to the Special Issue Viral Infection of Neural Stem Cells)
The Zika virus (ZIKV) has shown a promising oncolytic effect against embryonal CNS tumors. However, studies on the effect of different administration routes and the ideal viral load in preclinical models are highly relevant aiming for treatment safety and efficiency. Here, we investigated the effect and effectiveness of different routes of administration, and the number of ZIKVBR injections on tumor tropism, destruction, and side effects. Furthermore, we designed an early-stage human brain organoid co-cultured with embryonal CNS tumors to analyze the ZIKVBR oncolytic effect. We showed that in the mice bearing subcutaneous tumors, the ZIKVBR systemically presented a tropism to the brain. When the tumor was located in the mice’s brain, serial systemic injections presented efficient tumor destruction, with no neurological or other organ injury and increased mice survival. In the human cerebral organoid model co-cultured with embryonal CNS tumor cells, ZIKVBR impaired tumor progression. The gene expression of cytokines and chemokines in both models suggested an enhancement of immune cells recruitment and tumor inflammation after the treatment. These results open new perspectives for virotherapy using the ZIKVBR systemic administration route and multiple doses of low virus load for safe and effective treatment of embryonal CNS tumors, an orphan disease that urges new effective therapies. View Full-Text
Keywords: virotherapy; ZIKA virus; CNS tumors; murine pre-clinical study; immune cytokine profile virotherapy; ZIKA virus; CNS tumors; murine pre-clinical study; immune cytokine profile
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MDPI and ACS Style

Ferreira, R.O.; Granha, I.; Ferreira, R.S.; Bueno, H.d.S.; Okamoto, O.K.; Kaid, C.; Zatz, M. Effect of Serial Systemic and Intratumoral Injections of Oncolytic ZIKVBR in Mice Bearing Embryonal CNS Tumors. Viruses 2021, 13, 2103. https://doi.org/10.3390/v13102103

AMA Style

Ferreira RO, Granha I, Ferreira RS, Bueno HdS, Okamoto OK, Kaid C, Zatz M. Effect of Serial Systemic and Intratumoral Injections of Oncolytic ZIKVBR in Mice Bearing Embryonal CNS Tumors. Viruses. 2021; 13(10):2103. https://doi.org/10.3390/v13102103

Chicago/Turabian Style

Ferreira, Raiane O., Isabela Granha, Rodolfo S. Ferreira, Heloisa d.S. Bueno, Oswaldo K. Okamoto, Carolini Kaid, and Mayana Zatz. 2021. "Effect of Serial Systemic and Intratumoral Injections of Oncolytic ZIKVBR in Mice Bearing Embryonal CNS Tumors" Viruses 13, no. 10: 2103. https://doi.org/10.3390/v13102103

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