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Phenotipic alterations induced by allogeneic exosomes on dendritic cells

Grant number: 13/24232-8
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): December 01, 2013
Effective date (End): November 30, 2014
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Graziela Gorete Romagnoli
Grantee:Rebeca Sayuri Salvucci Hama
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

The use of dendritic cells (DCs) in the cancer immunotherapy has shown to be promising and Food and Drug Administration (FDA) approved the first DCs vaccine for metastatic prostate cancer patients in 2010. DCs are able to trigger antitumor adaptive immunity through the adequate processing and presentation of tumor antigen associated with major histocompatibility complex (MHC) molecules for näive T lymphocytes. Furthermore, nanovesicles from DCs, such as exosomes (Exo), can be transferred to the other DCs, which has not been in contact with the antigen yet. This transfer of information can result in the generation of in vitro and in vivo tumor specific T lymphocyte response. We previously observed that treatment of monocytes with Exo from allogeneic DCs (Exo-alo) during the in vitro differentiation into DCs, induced an increased phenotype more intensively than TNF-a used as a positive control of activation/maturation. Therefore, we hypothesized that Exo from healthy donors would be able to transfer the MHC-tumor peptide complex to allogeneic DCs increasing their immunogenicity and ability to initiate an effective antitumor response. Thereby in this study we aim to evaluate if the treatment of DCs with Exo-alo is able to modify the phenotype of these cells, increasing the expression of molecules involved in the lymphocytes activation. In addition, we intend to evaluate if these phenotype modifications is detectable in exosomes secreted by DCs treated with Exo-alo.