Active immunotherapy based on dendritic cells combined with chemotherapy in the treatment of advanced tumors associated with HPV-16

• Grant number: 21/03326-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: January 01, 2022
• End date: December 31, 2023
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Luis Carlos de Souza Ferreira
• Grantee: Karine Bitencourt Victorelli
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cervical cancer stands out due to the high mortality rate worldwide. Despite the available treatments, cervical cancer is still considered a public health problem and new therapeutic approaches are needed. The objective of this project is to evaluate a treatment composed of immunotherapy based on bone marrow differentiated dendritic cells (BMDCs) activated in vitro by the recombinant protein gDE7, in consortium with chemotherapeutic agents commonly used in the clinic, such as cisplatin, against HPV-16 associated tumors in advanced stages of development. This strategy aims to enhance therapeutic antitumor protection and potentiate the cellular interactions required to induce a specific effector immune response. The protein used for the activation of BMDCs refers to the fusion of glycoprotein D from herpes simplex virus type 1 (HSV-1) to oncoprotein E7 from HPV-16 (gDE7). To achieve the proposed object, we will use the model based on TC-1 tumor cells, implanted in the subcutaneous compartment or in mucosa of C57BL/6 mice. We will evaluate the effect of different doses of BMDC-based immunotherapy in association with the chemotherapeutic agent cisplatin. Once the optimal immunization conditions are established, the following parameters will be evaluated: the immunotherapeutic potential of the combined treatment; the activation of antigen-specific lymphocytes, both in the tumor microenvironment and systemically; the effect of the treatment on tumor-mediated immunosuppression; the generation of immune memory response and the toxicity of the treatment. We hope to generate data that will contribute to the establishment of an effective treatment based on the combination of active immunotherapy (BMDCs) consorting with conventional methodologies (chemotherapy) and that can be easily applied in clinical conditions.

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)