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| Author(s): |
Jamile Ramos da Silva
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2021-12-02 |
| Examining board members: |
Luis Carlos de Souza Ferreira;
Silvia Beatriz Boscardin;
Patricia Pereira Coltri;
Paula Ordonhez Rigato
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| Advisor: | Luis Carlos de Souza Ferreira |
| Abstract | |
Cervical cancer caused by persistent human papillomavirus (HPV) is a major cause of cancer deaths in women and the development of safe and effective immune therapeutic strategies represent a high priority. Particularly, HPV-associated tumors express constitutively E6 and E7 oncoproteins, excellent targets for the development of therapeutic vaccines. Given the paramount importance of developing active immunotherapies against these malignancies, we design a mRNA-based therapeutic vaccine lipid nanoparticles (LNP)-formulated encoding antigen gDE7, a fusion protein of herpes simplex virus type 1 glycoprotein D and HPV-16 E7 oncoprotein. Our results provide a proof of concept pre-clinical that with a single low-dose of the tested mRNA vaccines were capable to control tumors at different growth stages and generate memory T cell responses capable to prevent tumor relapses using TC-1 tumor model. Additionally, our vaccines generate robust activation of E7-specific CD8+ T cells with cytotoxic activity. Most importantly, our vaccines induced complete eradication of tumor cells using two different orthotropic tumor models (vaginal and tongue). In summary, our findings demonstrate the potency of mRNA vaccines on the treatment of HPV-associated tumors and raise perspectives for future applications at clinical settings. (AU) | |
| FAPESP's process: | 16/11594-7 - Self-amplifying RNA as immunotherapeutic strategy for the control of tumors induced by HPV-16 |
| Grantee: | Jamile Ramos da Silva |
| Support Opportunities: | Scholarships in Brazil - Doctorate |