Safety, Tumor Reduction, and Clinical Impact of Zika Virus Injection in Dogs with Advanced-Stage Brain Tumors

Autor(es):Mostrar menos -

Kaid, Carolini ^[1] ; dos Santos Madi, Raquel Azevedo ^[2] ; Astray, Renato ^[3] ; Goulart, Ernesto ^[1] ; Caires-Junior, Luiz Carlos ^[1] ; Mitsugi, Thiago Giove ^[1] ; Ramos Moreno, Ana Carolina ^[4] ; Castro-Amarante, Maria Fernanda ^[4] ; Pereira, Lennon Ramos ^[4] ; Milazzotto Maldonado Porchia, Bruna Felicio ^[5] ; de Andrade, Thais Oliveira ^[1] ; Landini, Vivian ^[1] ; Sanches, Daniel Soares ^[6] ; Pires, Carolina Goncalves ^[6] ; Oliveira Tanioka, Rubens Koji ^[2] ; Pereira, Marcia C. L. ^[1] ; Barbosa, Igor Neves ^[1] ; Massoco, Cristina O. ^[7] ; de Souza Ferreira, Luis Carlos ^[4] ; Okamoto, Oswaldo Keith ^{[1, 8]} ; Zatz, Mayana ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Human Genome & Stem Cell Res Ctr HUG CEL, Inst Biosci, Cidade Univ, BR-05508009 Sao Paulo - Brazil

^[2] Hosp Vet Granja Viana, BR-06345410 Granja Viana - Brazil

^[3] Butantan Inst, BR-05503900 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Vaccine Dev Lab, BR-05508900 Sao Paulo - Brazil

^[5] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Lab Tumor Immunol, BR-05508900 Sao Paulo - Brazil

^[6] Vet Pathol Anat Ctr, BR-05376070 Sao Paulo - Brazil

^[7] Univ Sao Paulo, Sch Vet Med & Anim Sci, Dept Pathol, BR-05508270 Sao Paulo - Brazil

^[8] Hosp Israelita Albert Einstein, Hemotherapy & Cellular Therapy Dept, BR-05652900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: MOLECULAR THERAPY; v. 28, n. 5, p. 1276-1286, MAY 6 2020.
• Citações Web of Science: 0

Resumo

Malignant brain tumors are among the most aggressive cancers with poor prognosis and no effective treatment. Recently, we reported the oncolytic potential of Zika virus infecting and destroying the human central nervous system (CNS) tumors in vitro and in immunodeficient mice model. However, translating this approach to humans requires pre-clinical trials in another immunocompetent animal model. Here, we analyzed the safety of Brazilian Zika virus (ZIKV(BR)) intrathecal injections in three dogs bearing spontaneous CNS tumors aiming an anti-tumoral therapy. We further assessed some aspects of the innate immune and inflammatory response that triggers the anti-tumoral response observed during the ZIKV(BR) administration in vivo and in vitro. For the first time, we showed that there were no negative clinical side effects following ZIKV(BR) CNS injections in dogs, confirming the safety of the procedure. Furthermore, the intrathecal ZIKV(BR) injections reduced tumor size in immunocompetent dogs bearing spontaneous intracranial tumors, improved their neurological clinical symptoms significantly, and extended their survival by inducing the destruction specifically of tumor cells, sparing normal neurons, and activating an immune response. These results open new perspectives for upcoming virotherapy using ZIKV to destroy and induce an anti-tumoral immune response in CNS tumors for which there are currently no effective treatments. (AU)

• Processo FAPESP: 13/08028-1 - CEGH-CEL - Centro de Estudos do Genoma Humano e de Células-Tronco
• Beneficiário: Mayana Zatz
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs