Targeting antigens to dendritic cells as an immunotherapeutic strategy to control HPV-induced tumors

• Grant number: 18/07629-5
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: July 01, 2018
• End date: November 30, 2021
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Luis Carlos de Souza Ferreira
• Grantee: Mariângela de Oliveira Silva
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cervical Cancer is considered a major public health problem and is one of the leading causes of Cancer death in women. Virtually, all cases of Cervical Cancer, as well as growing evidences of anal tumors and head and Neck Cancer, are associated with Human Papillomavirus (HPV) infections, mainly by the HPV-16, the genotype most commonly related to tumors. The viral proteins E6 and E7 are responsible for cellular malignization and are present in all transformed cells and, therefore, represent ideal targets for the development of antigen-specific therapeutic approaches. In this project, we will explore an immunotherapeutic strategy against these tumors using the HPV-16 E7 oncoprotein fused to the anti-DEC205 antibody. The antibodies will be produced from the culture supernatants of transfected HEK293T eukaryotic cells. The anti-DEC205 hybrid antibodies will be tested by parenteral or mucosal administration combined with the adjuvant Poly I: C. The therapeutic properties of the formulation will be evaluated in mice transplanted with TC-1 cells that express the HPV-16 E6 and E7 oncoproteins, following subcutaneous cell injection or mucosal tumor cell graft. The induction of E7-specific immune responses mediated primarily by T CD8+ lymphocytes will be evaluated. The results obtained during this project will contribute to the development of a novel immunotherapeutic strategy to control tumors associated with HPV-16. (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)

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)

SILVA, MARIANGELA O.; ALMEIDA, BIANCA S.; SALES, NATIELY S.; DINIZ, MARIANA O.; APS, LUANA R. M. M.; RODRIGUES, KARINE B.; SILVA, JAMILE R.; MORENO, ANA C. R.; PORCHIA, BRUNA F. M. M.; SULCZEWSKI, FERNANDO B.; et al. Antigen Delivery to DEC205(+) Dendritic Cells Induces Immunological Memory and Protective Therapeutic Effects against HPV-Associated Tumors at Different Anatomical Sites. International Journal of Biological Sciences, v. 17, n. 11, p. 2944-2956, 2021. (18/26515-0, 18/07629-5, 15/16505-0, 16/00708-1, 18/07142-9)

ANDREATA-SANTOS, ROBERT; MACHADO, RAFAEL RAHAL GUARAGNA; DOS SANTOS ALVES, RUBENS PRINCE; SALES, NATIELY SILVA; SOARES, CAMILA PEREIRA; RODRIGUES, KARINE BITENCOURT; SILVA, MARIANGELA OLIVEIRA; FAVARO, MARIANNA TEIXEIRA DE PINHO; RODRIGUES-JESUS, MONICA JOSIANE; YAMAMOTO, MARCIO MASSAO; et al. Validation of Serological Methods for COVID-19 and Retrospective Screening of Health Employees and Visitors to the Sao Paulo University Hospital, Brazil. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 12, p. 8-pg., 2022-06-02. (20/08943-5, 16/20045-7, 21/05661-1, 14/50890-5, 16/23560-0, 15/02352-7, 20/06409-1, 17/24769-2, 16/14344-1, 18/23680-0, 20/10700-3, 18/07629-5, 18/07142-9)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SILVA, Mariângela de Oliveira. Targeting of antigens to dendritic cells as an immunotherapeutic strategy to control HPV-induced tumors.. 2021. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.