Analysis of the functional profile of dendritic cells of patients with cervical cancer as proof of concept of the immunostimulating effect of the TERAH-7 protein

• Grant number: 23/03338-4
• Support Opportunities: Research Grants - Innovative Research in Small Business - PIPE
• Start date: June 01, 2023
• End date: May 31, 2024
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Natiely Silva Sales
• Grantee: Natiely Silva Sales
• Company: Imunotera Soluções Terapêuticas Ltda. - EPP
• CNAE: Pesquisa e desenvolvimento experimental em ciências físicas e naturais ; Atividades de apoio à gestão de saúde
• City: São Paulo
• Associated researchers: Ana Carolina Ramos Moreno ; Luis Carlos de Souza Ferreira ; Maria Luiza Nogueira Dias Genta ; Maricy Tacla Alves Barbosa
• Associated scholarship(s): 23/06949-4 - Analysis of the functional profile of dendritic cells of patients with cervical cancer as proof of concept of the immunostimulating effect of the TERAH-7 protein, BP.PIPE

Abstract

Cervical cancer induced by HPV is a serious public health problem and represents the fourth most common type of cancer in women. Patients diagnosed with this type of cancer are treated with surgery, radio and/or chemotherapy. More recently, immunotherapies based on monoclonal antibodies were incorporated into the treatment of cervical cancer in an attempt to increase patient survival. However, these alternatives have reduced effectiveness in more advanced cases of the disease and, in addition, are associated with the induction of severe adverse effects. In this sense, ImunoTera Soluções Terapeuticas has developed an innovative therapeutic vaccine, which can be used as an alternative capable of teaching the immune system to fight cervical intraepithelial neoplasia (CIN) and tumors caused by HPV. This therapeutic vaccine is based on a recombinant protein composed of glycoprotein D (gD) of HSV-1 genetically fused to the oncoprotein E7 of HPV-16 (TERAH-7). In the preclinical phase, this vaccine promoted complete regression of tumors associated with HPV-16. When associated with cisplatin, the most widely used chemotherapy drug in the treatment of cervical cancer, TERAH-7 allowed the reduction of chemotherapy doses and showed superior efficacy results when compared to other therapeutic strategies against tumors associated with HPV. Dendritic cells (DCs) orchestrate the development of the immune response, whether in immunity or tolerance. In cancer, DCs may play a dysfunctional role that contributes to tumor evasion of the immune system. Considering the already demonstrated effect of TERAH-7 on dendritic cells, this phase I PIPE proposal aims to study the immunological profile of MoDCs from patients with cervical cancer at different stages, in view of exposure and in vitro sensitization with TERAH-7. The capacity of the TERAH-7 protein to induce the maturation/activation of these MoDCs will be evaluated, as well as the capacity of these cells to induce E7-specific lymphoproliferation. The demonstration of the stimulatory effect of TERAH-7 will represent the proof of concept that this protein can help reverse tumor-orchestrated immunosuppression processes and trigger antitumor responses in patients with cervical cancer. This proposal is unprecedented and could point to TERAH-7 as a possible ally in the treatment of cancer induced by HPV through the reprogramming of the immune system of cancer patients. (AU)