Effect of Serial Systemic and Intratumoral Injections of Oncolytic ZIKV(BR) in Mice Bearing Embryonal CNS Tumors

Author(s)

Ferreira, Raiane Oliveira ^[1] ; Granha, Isabela ^[1] ; Ferreira, Rodolfo Sanches ^[1] ; Bueno, Heloisa de Siqueira ^[1] ; Okamoto, Oswaldo Keith ^{[1, 2]} ; Kaid, Carolini ^[1] ; Zatz, Mayana ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biociencias, Ctr Estudos Genoma Humano & Celulas Tronco, Dept Genet & Biol Evolut, BR-05508090 Sao Paulo, SP - Brazil

^[2] Hosp Israelita Albert Einstein, Hemotherapy & Cellular Therapy Dept, BR-05652900 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: Viruses-Basel; v. 13, n. 10 OCT 2021.
• Web of Science Citations: 2

Abstract

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 ZIKV(BR) 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 ZIKV(BR) oncolytic effect. We showed that in the mice bearing subcutaneous tumors, the ZIKV(BR) 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, ZIKV(BR) 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 ZIKV(BR) 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.</p> (AU)

• FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
• Grantee: Mayana Zatz
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 19/27784-8 - Study of oncolytic virus on an in vitro model of glioblastoma developed in brain organoid
• Grantee: Rodolfo Sanches Ferreira
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 20/14109-8 - Study of the oncolytic effect of Zika Virus on cells in the central nervous system tumor micro-environment
• Grantee: Raiane de Oliveira Ferreira
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 18/16213-7 - Improvement of Zika virus oncolytic properties aiming central nervous system tumors treatment
• Grantee: Carolini Kaid Dávila
• Support Opportunities: Scholarships in Brazil - Post-Doctoral