Development of chimeric aptamers for inactivation of human regulatory T cells

• Grant number: 19/13573-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): August 01, 2019
• Effective date (End): February 28, 2021
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Marcio Chaim Bajgelman
• Grantee: Carolinne Tomarchio Fogagnolo
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovações (Brasil). Campinas , SP, Brazil

Abstract

Cancer is a disease in which cells acquire genetic alterations. The tumor may have characteristics that promote its growth, such as the escape of the immune system. This ability to evade the immunity is largely attributed to the existence of immunosuppressive mechanisms that regulate the balance between immunotolerance and immunovigilance, in order to avoid an autoimmune response of T cells sensitized with their own antigens. In the last decade, it has been observed a significant development of therapeutic strategies that act on mechanisms related to the control of immunotolerance in T cells, mediated by receptors such as CLTA-4 and PD1. The use of drugs that act on these receptors has revolutionized clinical therapy. In addition to these receptors, another important mechanism of immunosuppression is modulated by regulatory T cell activity. This cell population has the potential to inhibit T cell proliferation and antagonize the antitumor immune response. Our LNBio-CNPEM group develops a strategy for inactivation of Treg immunosuppressive activity based on chimeric aptamers, for intracellular delivery of RNAi molecules. We have previously observed in animal models the possibility of using these aptamers to potentiate the antitumor response mediated by the GVAX vaccine, providing an additive effect. In this project, we plan to develop chimeric aptamers to deliver these RNAi molecules to human cells. These molecules could be explored in the development of future approaches for the treatment of human cancer.

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)

MASCARELLI, DANIELE E.; ROSA, RHUBIA S. M.; TOSCARO, JESSICA M.; SEMIONATTO, ISADORA F.; RUAS, LUCIANA P.; FOGAGNOLO, CAROLINNE T.; LIMA, GABRIEL C.; BAJGELMAN, MARCIO C.. Boosting Antitumor Response by Costimulatory Strategies Driven to 4-1BB and OX40 T-cell Receptors. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, v. 9, JUN 30 2021. (19/13573-5, 19/04458-8, 18/16449-0)