Antigen targeting to dendritic cells as a strategy to improve the efficiency of immunotherapies to HPV-16-associated tumors.

• Grant number: 18/26515-0
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2019
• End date: June 30, 2021
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Luis Carlos de Souza Ferreira
• Grantee: Luis Carlos de Souza Ferreira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Ana Carolina Ramos Moreno ; Bruna Felício Milazzotto Maldonado Porchia Ribeiro ; Jose Alexandre Marzagão Barbuto ; Silvia Beatriz Boscardin

Abstract

Cervical cancer is the fourth most common type of cancer in women worldwide. Despite of the availability of prevention methods and therapeutic alternatives, , this type of cancer continues to be a global public health problem. Thus, the search for new therapeutic approaches is worldwide demand. . Targeting antigens to dendritic cells (DCs) is one of the most effective methods to activate antitumor immune responses. On the other hand, the genetic fusion of tumor antigens to proteins or monoclonal antibodies that recognize surface receptors on DCs may enhance the immunogenicity of tumor antigens. The present research project aims to study experimental strategies that target specific tumor antigens to DCs as an approach for the therapeutic control of tumors induced by human papilloma viruses (HPV). In particular, the present project aims to evaluate the therapeutic anti-tumor effects induced by formulations based on the type 1 herpes simplex virus (HSV-1) glycoprotein D (gD) and anti-DEC205 monoclonal antibody (mAb anti-DEC205), both fused to the HPV-16 E7 oncoprotein, using mouse bone marrow DCs (BM-DCs) and in human monocyte-derived DCs (Mo-DCs). Binding assays of gDE7 and mAb anti-DEC205 will be performed on BM-DCs and Mo-DCs, as well as the determination of DCs activation by these antigens. In addition, this project intends to evaluate immunotherapies based on BM-DCs in vitro sensitized with gDE7 or anti-DECE7 in the murine model of HPV-16-associated tumors (TC-1 cell line), and to correlate the therapeutic antitumor effects with the activation of specific immune responses. The results obtained during the present project will contribute to the rational development of novel immunotherapeutic strategies for the control HPV-16-induced tumors. (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)