Glycolipids incorporation to coloidal polimeric nanocarriers as alternative iNKT lymphocyte based immunotherapy

• Grant number: 17/12799-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: January 01, 2018
• End date: February 28, 2019
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Alexandre de Castro Keller
• Grantee: Michelangelo Bauwelz Gonzatti
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Invariant Natura Killer T lymphocytes (iNKT) are immune cells that recognize lipid antigens compexed into CD1D molecules. Alpha-GalactosylCeramide (a-GalCer) is the most studied agonist, with main feature being the capacity to rapidly induce secretion of several cytokines. This ability to potentiate immune responses has been demonstrated in different clinical and experimental studies. Although its use has been authorized in clinical trials for the treatment of tumor, the results are underwhelming. The major barrier to the use of a-GalCer as effective tumor therapy is the fact that after primary activation iNKT cells enter in an anergic state becoming incapable of responding to subsequent challenge. In this regard, there are evidences that the incorporation of a-GalCer to polymeric particles can avoid the anergy induction, suggesting a possible alternative for its therapeutical use. The project pretends to determine if colloidal polymeric nanocarriers (NPC) developed by the Instituto de Pesquisa Tecnológicas do Estado de São Paulo (IPT) are capable of adsorb a-GalCer, or analogue molecules, preserve its immunogenic activity on iNKT lymphocytes and avoid the development of anergy. Also, we intend to determine the potential of NPC/a-GalCer to permeate the skin barrier and increase the immunity against skin tumor, such as melanoma. (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)

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)