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Immunotherapy against human papillomavirus (HPV) induced tumors

Grant number: 11/51218-0
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): February 01, 2012
Effective date (End): January 31, 2016
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal Investigator:Luis Carlos de Souza Ferreira
Grantee:Mariana de Oliveira Diniz
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):13/09100-8 - Cellular immune response in mucosal sites induced by a DNA vaccine against HPV-Induced tumors, BE.EP.PD


Cervical cancer, the second cause of cancer death among women, is associated with human papillomavirus infections in more than 99% of the cases. For the last 9 years, we have been developing a new vaccine strategy against HPV induced tumors based on DNA vaccines capable of expressing HPV-16 E7 protein genetically fused to herpes simplex virus (HSV) glycoprotein D (gD) coadministered to a plasmid encoding interleukin-2 (IL-2). In animal model, the vaccine has shown antitumural effects with no parallel in the literature. The present project aims to prepare the vaccine for clinical testing, continue the studies regarding the mechanisms involved in the immune protection elicited in mice and to construo a bivalent vaccine formulation. The activities planned for the clinical trial (to be held at the Hospital das Clínicas (HC), USP in collaboration with Dr. Esper Kallás) involve the production of the vaccine under Good Manufacturing Practices (GMP), pre-clinical studies and the drafting of the Clinical Research Protocol. Studies in animal models will be conducted to better understand the mechanisms related to the antitumor protection aiming to elucidate the cellular populations responsible for the observed phenomenon. Finally, the project foresees the development of a therapeutic bivalent vaccine against the two main viraltypes involved in the induction of cancer in humans by incorporating genes that encode HPV-16 and HPV-18 E6 and E7 oncoproteins. At the end of the project, we hope to prove the efficacy and safety of the anticancer immunotherapy proposal and generate a vaccine suitable for human use. (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)
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)
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)

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Filed patent(s) as a result of this research project

ESPOROS DE BACILLUS SP., MÉTODO DE PREPARO DOS ESPOROS, MÉTODO DE PREPARO DE CARTUCHOS DE BIOBALiSTICA, E USOS DOS ESPOROS BR1020140096795 - Universidade de São Paulo (USP) . Julio Kravcuks Rozenfeld ; Luana Raposo de Moraes Aps ; Luis Calos de Souza Ferreira ; Maria Teresa Moura Maly ; Mariana de Oliveira Diniz ; Milene Tavares Batista - April 2014, 23