Development of biological nanoparticles to boost antitumor immunity

• Grant number: 19/04458-8
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2019
• End date: January 31, 2022
• 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

Immunotherapy approaches have revolutionized perspectives in the treatment of human cancer. Antibodies known as checkpoint inhibitors act on receptors constitutively expressed on lymphocytes, blocking immunosuppressive mechanisms that antagonize the antitumor response. In this way, boosting lymphocyte activity and potentiation of antitumor immune vigilance is stimulated. In recognition of their relevance, immune checkpoint inhibitors were the subject of the 2018 Nobel Prize for medicine. Despite the success of these inhibitors, there are still a number of cases of cancer that are not responsive to existing therapies. In this sense, it is justified the importance of research in this area of knowledge, with the aim of increasing the repertoire of resources available for therapeutics. Our proposal is to develop a new immunotherapy strategy based on the use of biological nanoparticles derived from extracellular vesicles. These vesicles can be multifunctional, decorated with ligands that make it possible to drive the tropism of the particle to the tumor site, stimulate the immune system, and enable the vehiculation of cytotoxic molecules to potentiate the elimination of tumor cells. The rationale for this project is derived from previous findings from our group in which we observed the biological importance of vesicles secreted by antitumor vaccines containing TNFSF receptor ligands. We found that these vesicles had immunomodulatory effects acting on the co-stimulation of T cells. Although these vesicles stimulated T cell activity, this effect was not restricted to the tumor site, since costimulatory particles were administered systemically, without tissue-specific targeting. In this project, we plan to drive the immunomodulatory effect to the tumor site, activating dendritic cells locally and then potentiating the antitumor immune response. (AU)

Scientific publications

(6)

(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)

CONSONNI, SILVIO R.; DE CARVALHO, ANNA C. P. V.; MAURO, ARTUR B.; FRANCHINI, KLEBER G.; BAJGELMAN, MARCIO C.. Lentiviral transduction of neonatal rat ventricular myocytes preserves ultrastructural features of genetically modified cells. VIROLOGY, v. 562, p. 190-196, OCT 2021. (17/21720-2, 19/04458-8, 10/17086-7, 12/13132-0)

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)

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)

PERONI, LUIS A.; TOSCARO, JESSICA M.; CANATELI, CAMILA; TONOLI, CELISA C. C.; DE OLIVERA, RENATA R.; BENEDETTI, CELSO E.; COIMBRA, LAIS D.; PEREIRA, ALEXANDRE BORIN; MARQUES, RAFAEL E.; PROENCA-MODENA, JOSE L.; et al. Serological Testing for COVID-19, Immunological Surveillance, and Exploration of Protective Antibodies. FRONTIERS IN IMMUNOLOGY, v. 12, AUG 19 2021. (19/04458-8, 19/15049-1)

MANRIQUE-RINCON, ANDREA J.; RUAS, LUCIANA P.; FOGAGNOLO, CAROLINNE T.; BRENNEMAN, RANDALL J.; BEREZHNOY, ALEXEY; CASTELUCCI, BIANCA; CONSONNI, SILVIO R.; GILBOA, ELI; BAJGELMAN, MARCIO C.. Aptamer-mediated transcriptional gene silencing of Foxp3 inhibits regulatory T cells and potentiates antitumor response. MOLECULAR THERAPY-NUCLEIC ACIDS, v. 25, p. 143-151, SEP 3 2021. (19/04458-8, 12/13132-0, 13/02041-6)

PALAMETA, SOLEDAD; MANRIQUE-RINCON, ANDREA J.; TOSCARO, JESSICA M.; SEMIONATTO, ISADORA F.; FONSECA, MATHEUS C.; ROSA, RHUBIA S. M.; RUAS, LUCIANA P.; OLIVEIRA, PAULO S. L.; BAJGELMAN, MARCIO C.. Boosting antitumor response with PSMA-targeted immunomodulatory VLPs, harboring costimulatory TNFSF ligands and GM-CSF cytokine. MOLECULAR THERAPY-ONCOLYTICS, v. 24, p. 13-pg., 2022-03-17. (15/01488-2, 19/04458-8)