Development of a Treg Immunotherapy approach based on chimeric aptamers to potentiate antitumor vaccines

• Grant number: 21/09107-9
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2022
• End date: July 31, 2024
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Marcio Chaim Bajgelman
• Grantee: Marcio Chaim Bajgelman
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil

Abstract

In the last decade, there has been a significant development of therapeutic therapies that act on the mechanisms associated to the control of immune tolerance in T cells, mediated by receptors such as CLTA-4 and PD1, also known as immune checkpoints. The use of checkpoint inhibitors revolutionized medical practice. Furthermore, another important lymphocyte immunosuppression mechanism is related to regulatory T cell activities. This cell population has the potential to inhibit T cell proliferation and antagonize the antitumor immune response. Our LNBio-CNPEM group developed a strategy for inactivating the immunosuppressive activity of Treg based on chimeric aptamers, for intracellular delivery of RNAi molecules for silencing the FoxP3 transcription factor. We have previously observed in animal models the possibility of using these aptamers to potentiate the antitumor response mediated by the GVAX antitumor vaccine, providing a significant additive effect. In this project, we plan to develop chimeric aptamers for delivering RNAi molecules to human FoxP3 inhibition. We will explore the activities of these aptamers combined to antitumor vaccines harboring immunomodulators such as GM-CSF and T cell costimulatory receptor ligands OX40L and 4-1BBL. This project would contribute to the exploration of new therapeutic strategies for the treatment of human cancer. (AU)