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 Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): March 01, 2018
• Effective date (End): August 31, 2021
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Jose Alexandre Marzagão Barbuto
• Grantee: Bruna Felício Milazzotto Maldonado Porchia Ribeiro
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

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. (AU)

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)

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, JAN 1 2021. (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)

DA SILVA, JAMILE RAMOS; RODRIGUES, KARINE BITENCOURT; PELEGRIN, GUILHERME FORMOSO; SALES, NATIELY SILVA; MURAMATSU, HIROMI; SILVA, MARIANGELA DE OLIVEIRA; PORCHIA, BRUNA F. M. M.; MORENO, ANA CAROLINA RAMOS; APS, LUANA RAPOSO M. M.; VENCESLAU-CARVALHO, ALEXIA ADRIANNE; et al. Single immunizations of self-amplifying or non-replicating mRNA-LNP vaccines control HPV-associated tumors in mice. Science Translational Medicine, v. 15, n. 686, p. 18-pg., 2023-03-08. (16/20045-7, 16/00708-1, 15/16505-0, 16/11594-7, 13/15360-2, 17/21358-1, 19/01523-3, 18/26515-0, 21/03326-0, 18/07629-5, 16/14344-1)

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, 2022. (11/13805-1, 20/13640-1, 11/20917-0, 17/21358-1, 13/15360-2, 15/16505-0, 18/08502-9)