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

• Grant number: 12/21027-1
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2013
• End date: October 31, 2015
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Ramon Kaneno
• Grantee: Ramon Kaneno
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated researchers: Auro del Giglio ; João Pessoa Araújo Junior

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. (AU)