Development of chimeric aptamers containing RNAi for target-directed modulation of human regulatory T cells and strengthening of the antitumor immune response.

• Grant number: 22/12320-9
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): January 01, 2023
• Effective date (End): December 31, 2024
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Marcio Chaim Bajgelman
• Grantee: Daniela Sayuri Mizobuti
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovações (Brasil). Campinas , SP, Brazil

Abstract

The therapeutic strategies of cancer based on immunotherapy aim to strengthen the activity of cells of the immune system and to inhibit mechanisms of immune tolerance that antagonize the elimination of tumor cells. Regulatory T cells (Treg) protect the body from developing autoimmune diseases, however, in the condition of neoplasia, they can make immunological surveillance difficult and impair effective antitumor immunity in patients. In this sense, different therapeutic approaches target the inhibition of Treg cells, in order to strengthen the antitumor response. Previous data from our research group demonstrate the possibility of using RNA aptamers fused to RNAi molecules to silence the FoxP3 transcription factor, inactivating the immunosuppressive phenotype of Treg. This strategy potentiated the therapeutic effect of antitumor vaccines, inducing significant elimination of tumor cells in immunocompetent animals challenged with syngeneic tumors. In this project, we plan to develop new Aptamer-RNAi molecules for silencing the FoxP3 transcription factor in human Treg cells. Inhibition of regulatory T cells will contribute to stimulate immunosurveillance and potentiation of the antitumor immune response, and may contribute to the development of new therapies for the treatment of human cancer.