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Immunotherapy involving the E7 oncoprotein and glycoprotein D (gD) of herpes virus in vaccine formulations designed to control papillomavirus-associated tumors

Grant number: 11/20917-0
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2012
Effective date (End): May 31, 2015
Field of knowledge:Biological Sciences - Microbiology - Applied Microbiology
Principal Investigator:Luis Carlos de Souza Ferreira
Grantee:Bruna Felício Milazzotto Maldonado Porchia Ribeiro
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cervical cancer is considered a major public health problem and a major cause of tumor-related deaths in women. Virtually all cases of cervical cancer, as well as an increasing proportion of tumors in the anal and head / neck areas, are associated with infection by human papillomavirus (HPV), of which the genotypes HPV-16 and 18 are the most commonly related to these tumors. In this project we will explore a therapeutic vaccine strategy against these tumors using a recombinant form of HPV-16 E7 oncoprotein fused to the glycoprotein D (gD) of HSV-1, a protein with properties of endogenous adjuvants, particularly for CD8 + T lymphocytes. The recombinant protein will be produced in Escherichia coli and insect cells infected with baculovirus for further purification. The recombinant protein will be tested as subunit vaccines for parenteral administration in combination with different adjuvants and immunomodulatory agents. The therapeutic properties of the vaccine formulations will be evaluated in mice challenged with TC-1 cells which express the E6 and E7 oncoproteins of HPV-16. The E7-specific immune responses mediated primarily by CD8 + T lymphocytes will also be measured. The results obtained during the execution of this project should contribute to the development of a novel vaccine strategy for the control of tumors induced by HPV-16. (AU)

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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)
MILAZZOTTO MALDONADO PORCHIA, BRUNA FELICIO; DE MELO MORAES APS, LUANA RAPOSO; RAMOS MORENO, ANA CAROLINA; DA SILVA, JAMILE RAMOS; SILVA, MARIANGELA DE OLIVEIRA; SALES, NATIELY SILVA; DOS SANTOS ALVES, RUBENS PRINCE; REILY ROCHA, CLARISSA RIBEIRO; SILVA, MATHEUS MOLINA; RODRIGUES, KARINE BITENCOURT; et al. Active immunization combined with cisplatin confers enhanced therapeutic protection and prevents relapses of HPV-induced tumors at different anatomical sites. International Journal of Biological Sciences, v. 18, n. 1, p. 15-29, . (11/13805-1, 20/13640-1, 11/20917-0, 17/21358-1, 13/15360-2, 15/16505-0, 18/08502-9)
PORCHIA, BRUNA F. M. M.; MORENO, ANA CAROLINA R.; RAMOS, RODRIGO N.; DINIZ, MARIANA O.; DE ANDRADE, LAIS HELENA T. M.; ROSA, DANIELA S.; BARBUTO, JOSE ALEXANDRE M.; BOSCARDIN, SILVIA B.; FERREIRA, LUIS CARLOS S.. Herpes Simplex Virus Glycoprotein D Targets a Specific Dendritic Cell Subset and Improves the Performance of Vaccines to Human Papillomavirus-Associated Tumors. MOLECULAR CANCER THERAPEUTICS, v. 16, n. 9, p. 1922-1933, . (09/54599-5, 16/00708-1, 11/20917-0, 15/16505-0, 11/08905-7, 11/51218-0, 14/15061-8)
MORENO, ANA C. R.; PORCHIA, BRUNA F. M. M.; PAGNI, ROBERTA L.; SOUZA, PATRICIA DA CRUZ; PEGORARO, RAFAEL; RODRIGUES, KARINE B.; BARROS, TACITA B.; DE MELO MORAES APS, LUANA R.; DE ARAUJO, ELISEU F.; CALICH, VERA L. G.; et al. The Combined Use of Melatonin and an Indoleamine 2,3-Dioxygenase-1 Inhibitor Enhances Vaccine-Induced Protective Cellular Immunity to HPV16-Associated Tumors. FRONTIERS IN IMMUNOLOGY, v. 9, . (16/23189-0, 11/20917-0, 16/00708-1, 15/16505-0, 13/15360-2, 17/25544-4)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
RIBEIRO, Bruna Felício Milazzotto Maldonado Porchia. Immunotherapy and immunomodulation involving glycoprotein D (gD) of HSV-1 in vaccine formulations directed to HPV-16-associated tumors control.. 2015. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.

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