Characterization of dendritic cells used in an anti-HIV therapeutic vaccine clinical trial (Phase I/II)

• Grant number: 12/18879-6
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2012
• End date: November 30, 2015
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Telma Miyuki Oshiro Sumida
• Grantee: Telma Miyuki Oshiro Sumida
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Alberto José da Silva Duarte ; Alessandra Pontillo ; Alexandre de Almeida

Abstract

Immunotherapy based on monocyte-derived dendritic cells (MoDCs) is a promising strategy for the treatment of HIV-infected individuals. Due to its remarkable plasticity, heterogeneous populations of MoDCs can be obtained in vitro, depending on the culture conditions. Consequently, these cells could be differently able to secrete cytokines and to express molecules that participate in the process of antigen presentation (MHC, adhesion molecules and co-stimulatory), interfering with the profile and effectiveness of the immune response. Is currently underway in our laboratory a clinical trial of dendritic cell based immunetreatment for individuals chronically infected with HIV, free of antiretroviral therapy. The characterization of the DCs inoculated in the HIV subjetcs included in the study offers the rare opportunity to correlate phenotypic and functional aspects of DCs with the response to the DC-based immunotherapy in vivo. In this context, the aim of this study will be to characterize MoDCs of HIV-infected individuals included in the clinical trial with respect to (a) the expression of surface molecules, (b) the profile of cytokines produced, (c) the phagocytic ability, (d) the migratory ability, and (e) the ability to induce specific lymphocytes response. For this purpose several metodology will be used, such as flow citometry (extra- and intra-cellular), trans-well migration assay, co-culture of MoDCs and autologous lymphocytes. The data obtained from in vitro experiments will be correlated with the response to immunotherapy in patients within the on-going clinical trial. All together these results will provide evidence about the characteristics of MoDCs that could promote better response to vaccination, improving the design of novel DC-based therapy. (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)

DA SILVA, LAIS TEODORO; PONTILLO, ALESSANDRA; DA SILVA, WANESSA CARDOSO; DE ALMEIDA, ALEXANDRE; DA SILVA DUARTE, ALBERTO JOSE; OSHIRO, TELMA MIYUKI. Autologous and allogenic systems of HIV expansion: what is the better choice for clinical application in therapeutic vaccine?. Immunotherapy, v. 5, n. 12, p. 1305-1311, DEC 2013. (12/18879-6)

DA SILVA, LAIS TEODORO; DA SILVA, WANESSA CARDOSO; DE ALMEIDA, ALEXANDRE; REIS, DENISE DA SILVA; SANTLLO, BRUNA TERESO; RIGATO, PAULA ORDONHEZ; DA SILVA DUARTE, ALBERTO JOSE; OSHIRO, TELMA MIYUKI. Characterization of monocyte-derived dendritic cells used in immunotherapy for HIV-1-infected individuals. Immunotherapy, v. 10, n. 10, p. 871-885, AUG 2018. (12/18879-6, 12/17822-0)