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New therapeutic frontiers against tumors caused by human papilloma virus (HPV): experimental evaluation of the chemotherapy in association to vaccine strategies

Grant number: 13/15360-2
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): April 01, 2014
Effective date (End): July 31, 2018
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal researcher:Luis Carlos de Souza Ferreira
Grantee:Luana Raposo de Melo Moraes Aps
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Human papilloma virus (HPV) is responsible for 99,7% of cervical cancer cases and approximately 5% of all cancers worldwide, and HPV-16 is the main etiological agent of this disease. The development of therapies to control HPV-induced tumors searches the establishment of a new treatment based on immunotherapy that is advantageous compared with traditional invasive and aggressive procedures. In the field of immunotherapy, DNA vaccines represent a simple and promising strategy against HPV-associated tumors based on generating immune response against proteins known to be essential for malignant cell transformation. To potentiate this effect, the present project proposes the investigation of cisplatin association, the main chemotherapeutic drug currently used against cervical cancer to the vaccine plasmid pgDE7h that encodes E7 protein of HPV-16 fused to gD protein of Herpes Simplex Virus (HSV-1). The project also proposes the use of the formulation encapsulated in vesicles, of lipid or peptide nature, with goal of increasing the therapeutic efficacy of the vaccine and reduce the deleterious effects of the chemotherapy. The experiments will be based on the implantation of tumoral cell line (TC-1) in C57BL/6 mice and the therapeutic efficacy will be evaluated through monitoring of tumor regression and the cellular response induced by the combined therapy, including T lymphocytes CD4 + and specific CD8 + and production of important cytokines for the proliferative and cytotoxic activities, such as IL-2 and IFN-g. (AU)

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Scientific publications (4)
(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, . (11/51218-0, 13/15360-2, 15/16505-0, 14/11073-1, 16/11397-7, 16/14344-1, 16/00708-1)
AVILA, L. A.; APS, L. R. M. M.; PLOSCARIU, N.; SUKTHANKAR, P.; GUO, R.; WILKINSON, K. E.; GAMES, P.; SZOSZKIEWICZ, R.; ALVES, R. P. S.; DINIZ, M. O.; et al. Gene delivery and immunomodulatory effects of plasmid DNA associated with Branched Amphiphilic Peptide Capsules. JOURNAL OF CONTROLLED RELEASE, v. 241, p. 15-24, . (13/15360-2)
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)
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)
APS, Luana Raposo de Melo Moraes. New therapeutic frontiers against tumors caused by human papillomavirus (HPV): experimental evaluation of the association of chemotherapy with vaccine strategies.. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.

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