Clinical Trial
doi: 10.1016/j.clim.2009.09.009. Epub 2009 Nov 4.Immunologic activity and safety of autologous HIV RNA-electroporated dendritic cells in HIV-1 infected patients receiving antiretroviral therapy
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- PMID:19889582
- PMCID: PMC2818410
- DOI: 10.1016/j.clim.2009.09.009
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Clinical Trial
Immunologic activity and safety of autologous HIV RNA-electroporated dendritic cells in HIV-1 infected patients receiving antiretroviral therapy
Jean-Pierre Routy et al. Clin Immunol.2010 Feb.
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Abstract
Immunogenicity, manufacturing feasibility, and safety of a novel, autologous dendritic cell (DC)-based immunotherapy (AGS-004) was evaluated in ten human immunodeficiency virus type 1 (HIV-1)-infected adults successfully treated with antiretroviral therapy (ART). Personalized AGS-004 was produced from autologous monocyte-derived DCs electroporated with RNA encoding CD40L and HIV antigens (Gag, Vpr, Rev, and Nef) derived from each subjects' pre-ART plasma. Patients received monthly injections of AGS-004 in combination with ART. AGS-004 was produced within a mean of 6 weeks and yielded 4-12 doses/subject Full or partial HIV-specific proliferative immune responses occurred in 7 of 9 evaluable subjects. Responses were specific for the AGS-004 presented HIV antigens and preferentially targeted CD8(+) T cells. Mild adverse events included flu-like symptoms, fatigue, and injection site reactions. No evidence of autoimmunity, changes in viral load, or significant changes in absolute CD4(+) and CD8(+) T cell counts were observed. This pilot study supports the further clinical investigation of AGS-004.
Copyright 2009 Elsevier Inc. All rights reserved.
Figures
Heat map for proliferative response to AGS-004 HIV antigens for all evaluable subjects. Values represent the difference between eGFP control plus 3SD and HIV antigen induced CD8+ or CD4+ T cell proliferation at baseline, 4, 8 and 12 weeks derived from triplicate cultures. Colors represent a linear distribution of the data where blue corresponds to the lowest value (0.00) and red is the highest value (26.87), observed. N/A= not available
AbsoluteCD4+ T cell counts for all subjects throughout the study. Numbers adjacent to gray lines correspond to subject numbers in Tables 1 and 2. Black squares represent the median values at each time point.
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