Incorporation of glycosphingolipids into nanoparticles to immunotherapy using invariant Natural Killer T lymphocytes

• Grant number: 16/02189-1
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2016
• End date: January 31, 2019
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Alexandre de Castro Keller
• Grantee: Alexandre de Castro Keller
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Adriano Marim de Oliveira ; Bruno Camolese Vivanco ; Joes Nogueira Neto ; Marcelo Andrade de Lima ; Natália Neto Pereira Cerize

Abstract

Although immunotherapy is an alternative to a large number of diseases mediated by the immune system, the use of specific agonists to the invariant Natural Killer T (iNKT) lymphocytes remains neglected.One of these antagonists, the alfa-Galactosylceramide (a-GalCer), has been used in clinical trials, however, despite positive results, its efficiency is underwhelming. This contradiction may be partially explained by iNKT deficient activation due to structural alterations of low bio disponibility because of systemic administration of a-GalCer. Thus, an important challenge to the use of iNKT agonists is the development of an efficient delivery system.Because there is evidence that nanoparticles are useful tools to the transcutaneous drug delivery, our hypothesis is that the a-GalCer incorporation into these molecules can allow it transport to the deepest skin layers, where it can activate the iNKT cells both in the tumor microenvironment and in the draining lymph nodes. To test this idea, we intend to use a murine melanoma model.Thus, this project contributes to the development of new tools to iNKT-based immunotherapy and open new perspectives for the treatment of immune-mediated diseases. (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)

NOGUEIRA-NETO, JOES; LOURES, FLAVIO V.; SCHANOSKI, ALESSANDRA S.; ANDRADE, DAVID A. G.; GONZATTI, MICHELANGELO B.; COSTA, TANIA A.; VIVANCO, BRUNO C.; XANDER, PATRICIA; ROSA, DANIELA S.; CALICH, VERA L. G.; et al. Invariant Natural Killer T Cells as Key Players in Host Resistance against Paracoccidioides brasiliensis. JOURNAL OF IMMUNOLOGY RESEARCH, v. 2021, APR 16 2021. (16/02189-1, 16/23189-0, 12/04692-1, 11/51258-2)

GONZATTI, MICHELANGELO BAUWELZ; PERRUD SOUSA, MARIA EDUARDA; TUNISSI, ARIANE SIMOES; MORTARA, RENATO ARRUDA; DE OLIVEIRA, ADRIANO MARIM; PEREIRA CERIZE, NATALIA NETO; KELLER, ALEXANDRE DE CASTRO. Nano spray dryer for vectorizing alpha-galactosylceramide in polymeric nanoparticles: A single step process to enhance invariant Natural Killer T lymphocyte responses. International Journal of Pharmaceutics, v. 565, p. 123-132, JUN 30 2019. (16/02189-1, 17/12799-4, 16/15000-4)

PEREZ, ELIZABETH CRISTINA; XANDER, PATRICIA; LUCATELLI LAURINDO, MARIA FERNANDA; NOVAES E BRITO, RONNI ROMULO; VIVANCO, BRUNO CAMOLESE; MORTARA, RENATO ARRUDA; MARIANO, MARIO; LOPES, JOSE DANIEL; KELLER, ALEXANDRE CASTRO. The axis IL-10/claudin-10 is implicated in the modulation of aggressiveness of melanoma cells by B-1 lymphocytes. PLoS One, v. 12, n. 11, NOV 16 2017. (11/50256-6, 16/02189-1)