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Antitumor therapeutic potential of dendritic cells sensitized with allogeneic exosomes loaded with prostatic peptides

Grant number: 12/20494-5
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): September 01, 2013
Effective date (End): December 31, 2016
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Ramon Kaneno
Grantee:Graziela Gorete Romagnoli
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

The immunologic tolerance to tumors antigens in cancer patients is one of the main challenges in immunotherapy. Aiming to overcome this tolerance, clinical protocols with dendritic cells (DCs) have been developed, since they are able to induce tumor specific T lymphocyte response. Several approaches have been proposed to improve DCs antigen presentation capacity, including the use of exosomes loaded with relevant tumor antigens. Exosomes (Exo) are nanovesicles containing genetic material, MHC/peptides complexes, as well as costimulatory molecules, and can transfer these informations to other cell types. We hypothesized that DCs from healthy donors process antigens efficiently for presenting them in the MHC context and are also able to secreted them by Exo. Therefore, this study was designed to evaluate if DCs from prostate cancer patients treated with Exo of healthy donors, loaded with tumor peptides, show enhanced antigen presentation ability. Moreover, the allogeneic nature of Exo can have adjuvant effect for the sensitization of patients' DCs. Considering the regulatory role of CTLA-4 molecule, we also aim to evaluate it the association of antibody anti-CTLA-4 with the proposed protocol can potentiate the activity of effector T lymphocytes against of tumor. Therefore, our objective is to investigate if the treatment with allogeneic Exo increases the immunogenicity of DCs from healthy donors and patients, evaluating the modifications of their phenotype, expression of genes related with antigen presentation and lymphostimulatory functions. Besides, we will investigate if the capacity of these cells in stimulated T lymphocytes is further enhanced by their pretreatment with anti-CTLA-4.

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)
DE ALMEIDA, CAROLINA V.; ZAMAME, JOFER A.; ROMAGNOLI, GRAZIELA G.; RODRIGUES, CECILIA P.; MAGALHAES, MARIANNA B.; AMEDEI, AMEDEO; KANENO, RAMON. Treatment of colon cancer cells with 5-fluorouracil can improve the effectiveness of RNA-transfected antitumor dendritic cell vaccine. ONCOLOGY REPORTS, v. 38, n. 1, p. 561-568, JUL 2017. Web of Science Citations: 4.

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