Study of oncolytic virus on an in vitro model of glioblastoma developed in brain organoid

• Grant number: 19/27784-8
• Support type: Scholarships in Brazil - Master
• Effective date (Start): July 01, 2020
• Effective date (End): February 28, 2022
• Field of knowledge: Biological Sciences - Genetics
• Principal researcher: Oswaldo Keith Okamoto
• Grantee: Rodolfo Sanches Ferreira
• Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cancer is one of the leading causes of death in the world. In Brazil, there is an estimated 5,810 new cases of central nervous system (CNS) cancer in men and 5,510 new cases in women, by 2019. Although relatively rare, these CNS neoplasms are responsible for high morbidity and mortality rates. Gliomas are primary brain tumors originating from stem cells or neuroglial progenitors. Among the gliomas, the most frequent and with worst prognostic is glioblastoma (GBM), which has a highly heterogeneous histological pattern, where interactions between neoplastic and stromal tissues occur. Organoids are recent 3D cell culture models that, when compared to 2D cultures, better mimic the tumor microenvironment, allowing studies of cell behavior throughout development, cell-cell interactions, tissue organization, and drug response. Oncolytic viral therapy has emerged as an alternative strategy for treating aggressive cancers. Zika virus (ZIKV) selectively and significantly kills tumor strains of aggressive CNS embryonic cancers in vitro and in vivo and reduces the proliferation and self-renewal capacity of GBM glioma stem cells (GSCs). GSCs are primarily responsible for therapeutic resistance in GBM, which, added to the difficulty in maximal surgical resection, leads to a high relapse rate in treated patients. Considering the need for new treatment strategies of these high-grade gliomas, the great therapeutic potential of ZIKV, and the fitness of organoid models to study cancer, this study aims to develop brain organoids from human induced pluripotent stem cells (hiPSCs), both isolated and co-cultivated with GBM neurospheres, and subsequent ZIKVBR infection. The results are expected to help in understanding the invasive properties of three different GBM strains, in elucidating the therapeutic potential of ZIKV and in finding more efficient treatments for these aggressive neoplasms. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FERREIRA, RAIANE OLIVEIRA; GRANHA, ISABELA; FERREIRA, RODOLFO SANCHES; BUENO, HELOISA DE SIQUEIRA; OKAMOTO, OSWALDO KEITH; KAID, CAROLINI; ZATZ, MAYANA. Effect of Serial Systemic and Intratumoral Injections of Oncolytic ZIKV(BR) in Mice Bearing Embryonal CNS Tumors. Viruses-Basel, v. 13, n. 10, OCT 2021. (13/08028-1, 19/27784-8, 20/14109-8, 18/16213-7)