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

Autor:	Kaid C; Human Genome and Stem Cell Research Center (HUG-CEL) Institute of Biosciences, University of São Paulo, Cidade Universitária, São Paulo 055080-090, Brazil., Madi RADS; Hospital Veterinário Granja Viana, Granja Viana 06345-410, Brazil., Astray R; Butantan Institute, São Paulo 05503-900, Brazil., Goulart E; Human Genome and Stem Cell Research Center (HUG-CEL) Institute of Biosciences, University of São Paulo, Cidade Universitária, São Paulo 055080-090, Brazil., Caires-Junior LC; Human Genome and Stem Cell Research Center (HUG-CEL) Institute of Biosciences, University of São Paulo, Cidade Universitária, São Paulo 055080-090, Brazil., Mitsugi TG; Human Genome and Stem Cell Research Center (HUG-CEL) Institute of Biosciences, University of São Paulo, Cidade Universitária, São Paulo 055080-090, Brazil., Moreno ACR; Vaccine Development Laboratory, Biomedical Sciences Institute, Department of Microbiology, University of São Paulo, São Paulo 05508-900, Brazil., Castro-Amarante MF; Vaccine Development Laboratory, Biomedical Sciences Institute, Department of Microbiology, University of São Paulo, São Paulo 05508-900, Brazil., Pereira LR; Vaccine Development Laboratory, Biomedical Sciences Institute, Department of Microbiology, University of São Paulo, São Paulo 05508-900, Brazil., Porchia BFMM; Laboratory of Tumor Immunology, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-900, Brazil., de Andrade TO; Human Genome and Stem Cell Research Center (HUG-CEL) Institute of Biosciences, University of São Paulo, Cidade Universitária, São Paulo 055080-090, Brazil., Landini V; Human Genome and Stem Cell Research Center (HUG-CEL) Institute of Biosciences, University of São Paulo, Cidade Universitária, São Paulo 055080-090, Brazil., Sanches DS; Veterinary Pathological Anatomy Center. São Paulo 05376-070, Brazil., Pires CG; Veterinary Pathological Anatomy Center. São Paulo 05376-070, Brazil., Tanioka RKO; Hospital Veterinário Granja Viana, Granja Viana 06345-410, Brazil., Pereira MCL; Human Genome and Stem Cell Research Center (HUG-CEL) Institute of Biosciences, University of São Paulo, Cidade Universitária, São Paulo 055080-090, Brazil., Barbosa IN; Human Genome and Stem Cell Research Center (HUG-CEL) Institute of Biosciences, University of São Paulo, Cidade Universitária, São Paulo 055080-090, Brazil., Massoco CO; Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo 05508-270, Brazil., Ferreira LCS; Vaccine Development Laboratory, Biomedical Sciences Institute, Department of Microbiology, University of São Paulo, São Paulo 05508-900, Brazil., Okamoto OK; Human Genome and Stem Cell Research Center (HUG-CEL) Institute of Biosciences, University of São Paulo, Cidade Universitária, São Paulo 055080-090, Brazil; Hemotherapy and Cellular Therapy Department, Hospital Israelita Albert Einstein, São Paulo 05652- 900, Brazil., Zatz M; Human Genome and Stem Cell Research Center (HUG-CEL) Institute of Biosciences, University of São Paulo, Cidade Universitária, São Paulo 055080-090, Brazil. Electronic address: mayazatz@usp.br.
Jazyk:	angličtina
Zdroj:	Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2020 May 06; Vol. 28 (5), pp. 1276-1286. Date of Electronic Publication: 2020 Mar 10.
DOI:	10.1016/j.ymthe.2020.03.004
Abstrakt:	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. (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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