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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 type:Regular Research Grants
Duration: July 01, 2019 - June 30, 2021
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Luis Carlos de Souza Ferreira
Grantee:Luis Carlos de Souza Ferreira
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. 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)