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Exploration of molecular targets to inhibit regulatory T cells and potentiate antitumoral immunity

Grant number: 12/13132-0
Support type:Regular Research Grants
Duration: November 01, 2012 - October 31, 2014
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Marcio Chaim Bajgelman
Grantee:Marcio Chaim Bajgelman
Home Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia, Inovações e Comunicações (Brasil). Campinas , SP, Brazil

Abstract

Regulatory T cells (Treg) have the unique property of suppressing the proliferation of effector T cells, promoting immunological tolerance. Clinical samples isolated from patients revealed that the infiltrate of Tregs in the tumoral site correlates with the progression of cancer. Literature data suggest that elimination of Treg cells may act in synergy with other anticancer therapies. Among the most popular strategies, regulatory T cells can be inactivated by depletion, using antibodies or toxins directed to IL-2 receptor (CD25), however, the depletion mechanism mediated by CD25 receptor isn't specific and also causes the elimination of other CD25 positive cell populations, such as CD4 effector T cells that could contribute to antitumor immunity.In this project, we plan to explore molecular mechanisms to inhibit specific targets associated to the establishment and maintenance of the suppressor phenotype of regulatory T cells. We are going to generate RNA interference molecules (RNAi) to silence the expression of target genes with high specificity and high efficiency. These RNAi molecules will be delivered in vitro, using retroviral vectors, to verify inhibition of suppressive phenotype of Tregs. Additionally, we also are going to develop a non-viral platform based on chimerical RNA aptamers, that can be used to deliver inhibitory molecules in vivo through cell surface receptors on regulatory T cells. The RNA aptamers have low immunogenicity, high selectivity and allow in vivo application. We expect that the inactivation of the molecular targets of this study leads to the functional blocking, enhancing the antitumor immune response in animals challenged.In this way, mechanisms and platforms explored in this project can contribute to the development of potential strategies to enhance antitumor therapies. (AU)

Articles published in Agência FAPESP Newsletter about the research grant
Scientists create viral vector to boost immunity to 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)
MANRIQUE-RINCON, ANDREA J.; BERALDO, CAMILA M.; TOSCARO, JESSICA M.; BAJGELMAN, MARCIO C. Exploring Synergy in Combinations of Tumor-Derived Vaccines That Harbor 4-1BBL, OX40L, and GM-CSF. FRONTIERS IN IMMUNOLOGY, v. 8, SEP 19 2017. Web of Science Citations: 1.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.