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| Author(s): |
Júlia de Carvalho Nakamura
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina Veterinária e Zootecnia (FMVZ/SBD) |
| Defense date: | 2022-06-01 |
| Examining board members: |
Cristina de Oliveira Massoco Salles Gomes;
Paulo Eduardo Brandão;
Joaquim Aparecido Machado
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| Advisor: | Cristina de Oliveira Massoco Salles Gomes |
| Abstract | |
Progressively growing, visible tumors have evolved mechanisms to evade immune recognition and/or destruction. The ability of Newcastle Disease Virus (NDV) to infect and modify cancer cells, along with its ability to provide “danger signals ” to the immune system have been studied for decades in humans and promising outcomes have been reported in cancer patients. In Veterinary Medicine, immunotherapeutic interventions are rare and there is no information about NDV vaccine strains as therapeutic agents for cancer in dogs. Given the socioeconomic and regulatory scenarios in Brazil, one approach to decrease substantial costs and hasten the process of drug discovery to make it more accessible is called drug repurposing, where approved drugs are used to treat or prevent other diseases based on their mechanisms of action. Therefore, this research project rests on three pillars: Accessibility, Virology and Immuno- Oncology. Using two canine melanoma primary cell cultures (MeLn and GAB), we tested the oncolytic ability of two NDV vaccine strains (NDV1 e NDV2). Morphological analysis of infected cells and flow cytometry data showed that extremely low infectious doses caused cytopathic effects and induced cell death in MeLn and GAB cells. GAB cells were more susceptible to both viruses compared to MeLn. Gene expression analysis of MDA5, RIG-I, IFNA and IFNB by RT-PCR suggests that GAB ’s susceptibility could be related to a lower magnitude of Type I Interferon response. We also hypothesized that higher susceptibility to NDV could be related to a higher density of sialic receptors on the cellular membrane, which are potential receptors for viruses from the Paramyxoviridae family and can be labeled with fluorescent lectins SNA and MAL-I. However, flow cytometry analysis showed that mean fluorescence intensity of MeLn and GAB cells stained with lectins was not related to viral susceptibility. Nevertheless, the binding pattern of MAL-I (heterogeneous or homogeneous) can be related to NDV1 oncolytic potential and should be investigated as a biomarker to predict a patient ’s response to viral therapy. (AU) | |
| FAPESP's process: | 18/18448-1 - Drug repurposing in veterinary oncology: in vitro investigation of oncolytic and immunostimulatory potential of avian vaccine viral strains for the treatment of canine melanoma |
| Grantee: | Júlia de Carvalho Nakamura |
| Support Opportunities: | Scholarships in Brazil - Master |