DEVELOPMENT OF ONCOLYTIC VIRUS EXPRESSING CXCL10 AND XCL2 FOR CANINE MELANOMA

• Grant number: 24/00139-3
• Support Opportunities: Scholarships in Brazil - Master
• Start date: June 01, 2024
• End date: March 31, 2025
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: Heidge Fukumasu
• Grantee: Amanda da Matta Santos
• Host Institution: Faculdade de Zootecnia e Engenharia de Alimentos (FZEA). Universidade de São Paulo (USP). Pirassununga , SP, Brazil
• Associated research grant: 22/09378-5 - Development of innovative therapies and diagnostic tools for veterinary oncology, AP.TEM

Abstract

Around 90% of oral melanomas in dogs are malignant and have a high rate of invasiveness with a propensity to metastatic to the lungs and regional lymph nodes. The life expectancy of animals affected by the disease is reduced, even after surgical treatment, reaching a maximum survival of 18 months. In this scenario, immunotherapy has shown promise and its success is precisely because it causes an adaptive immune response in patients capable of challenging the tumor in more complex ways. In this sense, oncolytic viruses have stood out among immunotherapies for cancer, as they represent, in addition to being an agent of replication and selective killing in tumor cells, an immunostimulatory platform capable of transforming the tumor microenvironment. The objective of this project is to develop and characterize a genetically modified Newcastle disease virus (NDV-GM) expressing CXCL10 and XCL2 for oncolytic therapy in canine oral melanomas. To this end, the virus will be produced on a reverse genetics platform established at LOCT-USP and characterized by complete sequencing of the viral genome, production in SPF embryonated eggs, expression of the chemokines CXCL10 and XCL2 and will have its oncolytic activity evaluated in oral melanoma cells and canine non-tumor cells in vitro. These results will inform future phase 1 clinical studies to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary in vivo efficacy.