Phase 1 Clinical Trial of Oncolytic Virus NDV-GFP in Dogs

• Grant number: 24/11189-1
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: September 01, 2024
• End date: August 31, 2028
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Clinics and Surgery
• Principal Investigator: Heidge Fukumasu
• Grantee: Carolina Mariano Beraldo
• 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
• Associated scholarship(s): 25/23134-0 - OXC-101 clinical trial in dogs with lymphoma, haemangiosarcoma or mammary cancer., BE.EP.DD

Abstract

Genetically modified oncolytic viruses have been considered potential new therapies for cancer in humans and animals, as they are known to have greater selectivity to infect and kill cancer cells compared to non-cancerous host cells. Our research group has already demonstrated that the Newcastle Disease Virus genetically modified to express the green fluorescent protein (NDV-GFP) has had an oncolytic effect on cells from mammary tumors and dog melanoma, feline lymphoma and equine sarcoid to date. Based on the reverse genetics platform established in our laboratory, new candidates based on NDV are in the preparation and characterization phase. Therefore, there is an urgent need to define safety parameters and maximum tolerated dose in animals with cancer, in addition to evaluating pharmacokinetics and excretion, possibilities easily evaluated in a virus that expresses the green fluorescent protein when replicating in cells. Therefore, the objective of this project is to carry out a phase I clinical trial in dogs affected by malignant neoplasms, using NDV-GFP. For this, a 3+3 protocol will be carried out, which will have as primary goals the determination of safety and the maximum tolerated dose, and as secondary goals the characterization of the pharmacokinetics and preliminary efficacy of the treatment. The virus has already been produced in our laboratory, will be amplified and prepared for clinical use. Up to 20 dogs diagnosed with cancer will be selected, which will receive an initial dose of NDV, escalation will be carried out, and they will be clinically and laboratory evaluated. The results will be evaluated by statistical analysis.