New therapeutic frontiers against tumors caused by human papillomavirus (HPV): experimental evaluation of the association of chemotherapy with vaccine strategies.

Author(s)

Luana Raposo de Melo Moraes Aps

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2018-10-05

Examining board members

Luis Carlos de Souza Ferreira; Roger Chammas; Gabriel Padilla Maldonado; Enrique Mario Boccardo Pierulivo; Paula Ordonhez Rigato

• Advisor: Luis Carlos de Souza Ferreira

Abstract

The present study aimed to improve the antitumor effects of a new immunotherapeutic strategy for the control of tumors induced by human papillomavirus type 16 (HPV-16). For this purpose, a new concept of active immunotherapy based on a recombinant DNA vaccine developed at the Laboratory of Vaccine Development at USP (pgDE7h) was used, and different experimental approaches were designed to increase the therapeutic efficacy of the treatment. Thus, the present work focused on the development of new delivery systems for the DNA vaccine using three distinct nanocarregadores, of a lipid, protein or peptidic nature, and the evaluation of the therapeutic efficacy of these in front of pre-established tumors. The present study also evaluated the combination of pgDE7h-based immunotherapy with chemotherapy using the cisplatin compound to allow the treatment of tumors in more advanced stages of growth. The results demonstrate that the association of the peptide-vesicle vaccine plasmid was shown to activate murine dendritic cells in vitro and promote increased survival of animals against the subcutaneous tumor model without inducing toxicity. When combined with cisplatin treatment, the vaccine, mainly associated with electroporation, demonstrated a synergistic effect, promoting total tumor regression, expressive increase in the activation of CD8 E7-specific T lymphocytes, induction of effector and resident memory response and control of immunosuppressive populations in a systemic way and in the tumor microenvironment. In summary, the research expanded knowledge about the action of active immunotherapy against HPV-induced tumors and opened important perspectives for its use under clinical conditions. (AU)

• FAPESP's process: 13/15360-2 - New therapeutic frontiers against tumors caused by human papilloma virus (HPV): experimental evaluation of the chemotherapy in association to vaccine strategies
• Grantee: Luana Raposo de Melo Moraes Aps
• Support Opportunities: Scholarships in Brazil - Doctorate