Self-amplifying RNA as immunotherapeutic strategy for the control of tumors induced by HPV-16

• Grant number: 16/11594-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): October 01, 2016
• Effective date (End): November 30, 2021
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Luis Carlos de Souza Ferreira
• Grantee: Jamile Ramos da Silva
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 19/01523-3 - mRNA-based vaccines targeting HPV-induced tumors, BE.EP.DR

Abstract

Cervical cancer is the third leading cause of cancer death in women and is associated with persistent infection Human Papilloma Virus (HPV) by more than 99% of cases. Given the epidemiological importance of tumors induced by HPV and the paramount importance of developing active immunotherapies against these injuries during the past 12 years, we have developed a vaccine DNA-based therapeutic strategy encoding the E7 protein of HPV-16 fused to glycoprotein D ( gD) of Herpes Simplex Virus type 1 (HSV-1), called gDE7. Recently, solid evidence demonstrated that self-amplifying RNA can be an excellent platform for the development of human vaccines. This technology was able to induce a strong protective immune response in infectious disease control, consistent with DNA technology associated with electroporation, but without the inherent safety limitations. Although notable positive attributes of this highly innovative platform, its benefits as a therapeutic vaccine for cancer treatment have not been studied. This study aims to develop a self-amplifying RNA vaccine from gDE7 gene associated with liposomes targeted to tumor control induced by HPV-16. To improve the delivery of the vaccine to cells specialized in antigen presentation, we propose to use antibody targeting dendritic cells attached to the surface of the nanoparticles. In search of a model that is closest to what happens in the clinic will be evaluated the therapeutic potential of the new vaccine formulation to promote regression of tumors located at mucosal sites. The ability of the vaccine to elicit T lymphocyte response CD8 + E7-specific and systemic able to infiltrate the tumor site will be determined by various experimental approaches. The results obtained during the execution of this project will contribute to the development of a novel vaccine strategy in suitable conditions for their clinical use.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

RAMOS DA SILVA, JAMILE; RAMOS MORENO, ANA CAROLINA; SILVA SALES, NATIELY; DE OLIVEIRA SILVA, MARIANGELA; APS, LUANA R. M. M.; PORCHIA, BRUNA F. M. M.; BITENCOURT RODRIGUES, KARINE; CESTARI MORENO, NATALIA; VENCESLAU-CARVALHO, ALEXIA ADRIANNE; MENCK, CARLOS FREDERICO M.; et al. A therapeutic DNA vaccine and gemcitabine act synergistically to eradicate HPV-associated tumors in a preclinical model. ONCOIMMUNOLOGY, v. 10, n. 1, JAN 1 2021. (11/51218-0, 16/14344-1, 16/00708-1, 15/16505-0, 18/26555-2, 16/11397-7, 17/21358-1, 16/11594-7, 14/11073-1)

DA SILVA, JAMILE RAMOS; RODRIGUES, KARINE BITENCOURT; PELEGRIN, GUILHERME FORMOSO; SALES, NATIELY SILVA; MURAMATSU, HIROMI; SILVA, MARIANGELA DE OLIVEIRA; PORCHIA, BRUNA F. M. M.; MORENO, ANA CAROLINA RAMOS; APS, LUANA RAPOSO M. M.; VENCESLAU-CARVALHO, ALEXIA ADRIANNE; et al. Single immunizations of self-amplifying or non-replicating mRNA-LNP vaccines control HPV-associated tumors in mice. Science Translational Medicine, v. 15, n. 686, p. 18-pg., 2023-03-08. (16/20045-7, 16/00708-1, 15/16505-0, 16/11594-7, 13/15360-2, 17/21358-1, 19/01523-3, 18/26515-0, 21/03326-0, 18/07629-5, 16/14344-1)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SILVA, Jamile Ramos da. mRNA-based vaccines formulated in lipid nanoparticles against tumors induced by HPV.. 2021. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.