Immunotherapy and immunomodulation involving glycoprotein D (gD) of HSV-1 in vaccine formulations directed to HPV-16-associated tumors control.

Author(s)

Bruna Felicio Milazzotto Maldonado Porchia

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2015-11-25

Examining board members

Luis Carlos de Souza Ferreira; Bruna Cunha de Alencar Bargieri; Alexandre Salgado Basso; Enrique Mario Boccardo Pierulivo; Paula Ordonhez Rigato

• Advisor: Luis Carlos de Souza Ferreira

Abstract

Cervical cancer is considered a major public health problem and one of the leading causes of cancer death in women. The main goal of this thesis was the improvement of a therapeutic antitumor vaccine based on gDE7 protein in formulations admixed with adjuvants under experimental conditions with the tumor cell line TC-1. The gDE7 protein was expressed and purified from E. coli, and then tested in combination with different vaccine adjuvants. The gDE7 protein admixed with poly(I:C) conferred complete therapeutic antitumor protection to mice previously challenged with TC-1 cells and induced polyfunctional, cytotoxic E7-specific CD8+ T cells with effector/effector memory phenotype. It was also demonstrated that the gDE7 protein activated a specialized dendritic cell subset involved in specific antigen cross-presentation to CD8+ T cells, both in mice and humans. These results open perspectives for the use of the gD protein use as a vaccine platform for the control of HPV-16-induced tumors. (AU)

• FAPESP's process: 11/20917-0 - Immunotherapy involving the E7 oncoprotein and glycoprotein D (gD) of herpes virus in vaccine formulations designed to control papillomavirus-associated tumors
• Grantee: Bruna Felício Milazzotto Maldonado Porchia Ribeiro
• Support Opportunities: Scholarships in Brazil - Doctorate