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

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...

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Bibliographic Details
Published in:Viruses 2021-10, Vol.13 (10), p.2103
Main Authors: Ferreira, Raiane Oliveira, Granha, Isabela, Ferreira, Rodolfo Sanches, Bueno, Heloisa de Siqueira, Okamoto, Oswaldo Keith, Kaid, Carolini, Zatz, Mayana
Format: Article
Language:English
Subjects:
Animals
Ataxia
Brain
Brain tumors
Chemokines
CNS tumors
Cytokines
Gene expression
immune cytokine profile
Immunotherapy
Infections
murine pre-clinical study
Oncolysis
Organoids
Tropism
Tumor cells
Tumors
Viral infections
virotherapy
ZIKA virus
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Summary: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.
ISSN:1999-4915
1999-4915
DOI:10.3390/v13102103