Tissue evaluation of canine oral melanomas treated with gene therapy mediated by adenoviral vectors carrying p14ARF and Interferon-beta.

• Grant number: 23/01697-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2023
• End date: August 31, 2025
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Clinics and Surgery
• Principal Investigator: Bryan Eric Strauss
• Grantee: Jean Carlos dos Santos da Luz
• Host Institution: Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira (ICESP). Coordenadoria de Serviços de Saúde (CSS). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Brazil is increasingly well positioned to compete in the field of advanced therapies. In particular, five gene therapy products have been registered with ANVISA, paving the way for new proposals for clinical evaluation. Our group has invested the development of an intervention for melanoma that uses improved adenoviral vectors to deliver two genes, p14ARF and interferon-beta, which cooperate to induce immunogenic death and antitumor immune response, the subject of a recently approved patent. We have demonstrated the antitumor effects using murine, human and canine cell lines, but the in vivo evaluation is so far restricted to mouse models, known for their limited representation of the human clinical case. Considering that our approach is safe and has the potential to bring benefits to the patient, we are ready to take the next step in the translational development of our approach. We propose the application of our experimental intervention in spontaneous cases of oral melanoma in canine patients, as it is a model that more reliably recapitulates the development of cancers in humans when compared to murine models. The primary outcome proposed in this study is to investigate the safety and practice of performing gene therapy in dogs with melanoma in the oral cavity. The secondary outcome would be the exploration of the impact of gene therapy on tumor progression, activation of antitumor immune response and antiviral response. With the success of this project, we will open the way for future translational trials under suitable conditions to support the proposal of a formal clinical study, either in humans or in dogs.