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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Viruses-Basel; v. 13, n. 10 OCT 2021.
• Citações Web of Science: 2

Resumo

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)

• Processo FAPESP: 13/08028-1 - CEGH-CEL - Centro de Estudos do Genoma Humano e de Células-Tronco
• Beneficiário: Mayana Zatz
• Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 19/27784-8 - Estudo de vírus oncolítico em modelo in vitro de glioblastoma desenvolvido em organóide cerebral
• Beneficiário: Rodolfo Sanches Ferreira
• Linha de fomento: Bolsas no Brasil - Mestrado
• Processo FAPESP: 20/14109-8 - Estudo do efeito oncolítico do Vírus da Zika nas células do microambiente de tumores do sistema nervoso central
• Beneficiário: Raiane de Oliveira Ferreira
• Linha de fomento: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 18/16213-7 - Aprimoramento do potencial oncolítico do vírus ZIKA visando a terapia de tumores do sistema nervoso central
• Beneficiário: Carolini Kaid Dávila
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado