Engineering t cells harboring new transgenic TCRs isolated from tumor infiltrated lymphocytes in animals undergone therapeutic protocols using immunomodulators

• Grant number: 17/06692-2
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2017
• End date: August 31, 2019
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Marcio Chaim Bajgelman
• Grantee: Marcio Chaim Bajgelman
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Campinas , SP, Brazil

Abstract

The use of new strategies for treatment of cancer, based on immunotherapy have generated surprising results. Most of these strategies are driven to favor the activity of T cells, which are recognized to play an important role in the control and elimination of tumor cells. T cells have surface receptors that transduce signaling mediators of the activation state. The first activation signal depends on the interaction of the T cell receptor with the peptide-MHC complex on the surface of a presenting cell. Next, a second signal, independent of the MHC-peptide, is required for cell proliferation and differentiation. Other costimulatory signals can be mediated by surface receptors, favoring activation, proliferation and longevity. Data from the literature demonstrate the potential of using lymphocytes infiltrated at tumor sites for cancer therapy. These lymphocytes can be expanded in vitro and when reintroduced in other recipients, they allow the elimination of tumors. Alternatively, cloning TCRs of the Tumor Infiltrated T cells also allows the generation of antigen-specific T lymphocytes by viral vectors. These genetically modified lymphocytes can be efficiently used to eliminate tumor cells. In this work, we plan to explore the discovery of new T cell receptors from lymphocytes isolated from tumor sites in animals treated with immunomodulators and combinations that cause a great reduction in tumor mass. The results obtained in this project may contribute to the development of new therapeutic strategies for the treatment of human cancer. (AU)

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)

LOIOLA, LIVIA M. D.; BATISTA, MARINA; CAPELETTI, LARISSA B.; MONDO, GABRIELA B.; ROSA, RHUBIA S. M.; MARQUES, RAFAEL E.; BAJGELMAN, MARCIO C.; CARDOSO, MATEUS B.. Shielding and stealth effects of zwitterion moieties in double-functionalized silica nanoparticles. Journal of Colloid and Interface Science, v. 553, p. 540-548, OCT 1 2019. (17/09203-2, 15/25406-5, 16/21598-0, 17/01167-7, 17/06692-2, 16/16905-0)

MANRIQUE-RINCON, ANDREA J.; DE CARVALHO, ANNA C.; EUGENIA RIBEIRO DE CAMARGO, M.; FRANCHINI, KLEBER G.; BAJGELMAN, MARCIO C.. Development of a flow cytometry assay which allows to evaluate the efficiency of immunomodulatory vaccines to enhance T cell-mediated antitumor response. Journal of Biotechnology, v. 284, p. 11-16, OCT 20 2018. (17/06692-2, 13/02041-6)

SEMIONATTO, ISADORA FERRAZ; PALAMETA, SOLEDAD; TOSCARO, JESSICA MARCELINO; MANRIQUE-RINCON, ANDREA JOHANNA; RUAS, LUCIANA PEREIRA; PAES LEME, ADRIANA FRANCO; BAJGELMAN, MARCIO CHAIM. Extracellular vesicles produced by immunomodulatory cells harboring OX40 ligand and 4-1BB ligand enhance antitumor immunity. SCIENTIFIC REPORTS, v. 10, n. 1, p. 10-pg., 2020-09-16. (17/06692-2, 19/04458-8, 18/16449-0)