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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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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]
Número total de Autores: 7
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
Número total de Afiliações: 2
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