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

• Published in: Molecular therapy 2020-05, Vol.28 (5), p.1276-1286
• Main Authors: Kaid, Carolini, Madi, Raquel Azevedo dos Santos, Astray, Renato, Goulart, Ernesto, Caires-Junior, Luiz Carlos, Mitsugi, Thiago Giove, Moreno, Ana Carolina Ramos, Castro-Amarante, Maria Fernanda, Pereira, Lennon Ramos, Porchia, Bruna Felício Milazzotto Maldonado, de Andrade, Thais Oliveira, Landini, Vivian, Sanches, Daniel Soares, Pires, Carolina Gonçalves, Tanioka, Rubens Koji Oliveira, Pereira, Marcia C.L., Barbosa, Igor Neves, Massoco, Cristina O., Ferreira, Luís Carlos de Souza, Okamoto, Oswaldo Keith, Zatz, Mayana
• Format: Article
• Language: English
• Subjects: canine clinical trial; CNS tumors; immune cytokine profile; Original; virotherapy; ZIKA virus
• ISSN: 1525-0016; 1525-0024
• DOI: 10.1016/j.ymthe.2020.03.004

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 (ZIKVBR) 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 ZIKVBR administration in vivo and in vitro. For the first time, we showed that there were no negative clinical side effects following ZIKVBR CNS injections in dogs, confirming the safety of the procedure. Furthermore, the intrathecal ZIKVBR 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. [Display omitted] Malignant brain tumors are aggressive cancers. We show that Zika virus injected in dogs bearing advanced stage spontaneous CNS tumors aiming an anti-tumoral therapy reduced tumor size, sparing normal neurons and activating an immune response, improved dogs’ neurological clinical symptoms significantly, and extended their survival without adverse side effects.