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Control tumors induced by HPV -based immunotherapy in combination monoclonal antibodies blocking immunosuppressive pathways a therapeutic vaccine capable of activating CD8 + cytotoxic T lymphocytes

Grant number: 16/14344-1
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): October 01, 2016
Effective date (End): November 30, 2020
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal Investigator:Luis Carlos de Souza Ferreira
Grantee:Natiely Silva Sales
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Cervical cancer associated with persistent infections by human papilloma virus ( HPV) infection is a public health problem and is the third most frequent type of cancer in women. Patients diagnosed with HPV -induced tumors are treated with surgery, radiotherapy and chemotherapy , which have a lower rate of efficiency to more advanced stages of the disease and inducing severe adverse effects. Several studies seek to develop new therapies against cancer associated with HPV infection as the combination of chemotherapy and immunotherapeutic strategies that work in different mechanisms ( cell death , immunosuppression, specific antigen response induction). The establishment of an immunotherapy treatment capable of activating immune cells to act specifically on tumor cells may significantly influence the success of conventional therapies and improve the quality of life of patients. In Vaccine Development Laboratory (LDV) a DNA vaccine against tumors induced by HPV has been developed based on the expression of a hybrid protein result of gene fusion glycoprotein D (gD) of HSV-1 E7 oncoprotein of HPV-16 (pgDE7h ). In animal models, this vaccine has proved effective in inducing specific cytotoxic cellular response and control tumors expressing E6 and HPV-16 E7 (TC-1 cells). However, the clinical translation of the vaccine requires an increase in its power, mainly for the control of more advanced tumors. In the present work, we propose the development of a new immunotherapy based on the lock pool of monoclonal antibodies of "checkpoints" immune (anti-CTLA-4, anti-PD-1 and anti-PDL-1), and pgDE7h vaccine, aiming evaluate the antitumor activity in mice implanted with TC-1 cells subcutaneously or mucosal (oral or intravaginal).After the establishment of the immunization protocol , treatment will be associated with cisplatin chemotherapy , in order to verify a possible synergistic effect with standard therapy . the ability of different therapeutic protocols to activate antigen-specific immune responses and control the immunosuppressive response triggered by the tumor will be assessed . From the research proposal we hope to obtain data which contribute to the establishment of a novel therapy based on a combination of active immunotherapy ( DNA vaccines ) and passive ( monoclonal antibodies) that can be rapidly validated in clinical conditions .

Matéria(s) publicada(s) na Revista Pesquisa FAPESP sobre a bolsa::
Surge una posible vacuna contra el cáncer causado por el VPH 
Vaccine candidate designed to treat cancer caused by HPV 
News published in Agência FAPESP Newsletter about the scholarship:
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Scientific publications (5)
(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)
ANDREATA-SANTOS, ROBERT; MACHADO, RAFAEL RAHAL GUARAGNA; DOS SANTOS ALVES, RUBENS PRINCE; SALES, NATIELY SILVA; SOARES, CAMILA PEREIRA; RODRIGUES, KARINE BITENCOURT; SILVA, MARIANGELA OLIVEIRA; FAVARO, MARIANNA TEIXEIRA DE PINHO; RODRIGUES-JESUS, MONICA JOSIANE; YAMAMOTO, MARCIO MASSAO; et al. Validation of Serological Methods for COVID-19 and Retrospective Screening of Health Employees and Visitors to the Sao Paulo University Hospital, Brazil. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 12, p. 8-pg., . (20/08943-5, 16/20045-7, 21/05661-1, 14/50890-5, 16/23560-0, 15/02352-7, 20/06409-1, 17/24769-2, 16/14344-1, 18/23680-0, 20/10700-3, 18/07629-5, 18/07142-9)
SILVA, JAMILE R.; SALES, NATIELY S.; SILVA, MARIANGELA O.; APS, LUANA R. M. M.; MORENO, ANA C. R.; RODRIGUES, ELAINE G.; FERREIRA, LUIS C. S.; DINIZ, MARIANA O.. Expression of a soluble IL-10 receptor enhances the therapeutic effects of a papillomavirus-associated antitumor vaccine in a murine model. CANCER IMMUNOLOGY IMMUNOTHERAPY, v. 68, n. 5, p. 753-763, . (16/00708-1, 16/14344-1, 15/16505-0, 16/11397-7, 13/15360-2, 11/51218-0, 14/11073-1)
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, . (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., . (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)
PEREIRA, LENNON RAMOS; DOS SANTOS ALVES, RUBENS PRINCE; SALES, NATIELY SILVA; ANDREATA-SANTOS, ROBERT; VENCESLAU-CARVALHO, ALEXIA ADRIANNE; PEREIRA, SAMUEL SANTOS; CASTRO-AMARANTE, MARIA FERNANDA; RODRIGUES-JESUS, MONICA JOSIANE; DE PINHO FAVARO, MARIANNA TEIXEIRA; CHURA-CHAMBI, ROSA MARIA; et al. Enhanced Immune Responses and Protective Immunity to Zika Virus Induced by a DNA Vaccine Encoding a Chimeric NS1 Fused With Type 1 Herpes Virus gD Protein. FRONTIERS IN MEDICAL TECHNOLOGY, v. 2, p. 14-pg., . (14/17595-0, 16/20045-7, 16/23560-0, 18/14459-9, 16/05570-8, 18/08199-4, 17/09661-0, 16/14344-1)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)

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