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Human papillomavirus (HPV)-associated neoplasia: a new therapeutic approach based on active immunotherapy through targeted stimulation of dendritic cells

Grant number: 17/21358-1
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): March 01, 2018
Effective date (End): June 30, 2020
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Jose Alexandre Marzagão Barbuto
Grantee:Bruna Felício Milazzotto Maldonado Porchia Ribeiro
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Cervical cancer is the fourth most lethal type of cancer in women worldwide. Despite available treatments, cervical cancer remains a global public health problem. Therefore, the search for new therapeutic approaches for this type of cancer is a priority. This project aims to study the clinical-oncological and immunological parameters of patients with high-grade cervical intraepithelial neoplasia (CIN 2/3) or in situ carcinoma induced by HPV-16 or HPV-18 infection, undergoing a therapeutic procedure based on monocyte-derived dendritic cells (Mo-DCs) sensitized with Herpes simplex virus 1 glycoprotein D (gD), genetically fused to HPV-16 or HPV-18 E6 and E7 oncoproteins. The present project aims to evaluate the effect of the gDE6E7 protein on Mo-DCs of patients with CIN 2/3 or in situ carcinoma and to analyze the adaptive response mediated by these Mo-DCs. In parallel, experiments with the preclinical model of HPV-16-associated tumors will be conducted to elucidate the cellular mechanisms of the proposed immunotherapy. Finally, patients with CIN 2/3 or in situ carcinoma will undergo an immunotherapeutic treatment with autologous Mo-DCs sensitized with the gDE6E7 protein, associated with allogeneic Mo-DCs or other adjuvants, in a phase I/II clinical trials in the Hospital das Clínicas, USP. These patients will be monitored for evaluation of the phenotype and function of immune system cells present in the peripheral circulation. Therefore, this project intends to combine the basic/translational research performed at the ICB-USP and the clinical-oncological research carried out at the HC-USP, in order to generate data that could have a significant impact on the treatment of HPV-induced cancer.