TY - JOUR
T1 - Immunologic activity and safety of autologous HIV RNA-electroporated dendritic cells in HIV-1 infected patients receiving antiretroviral therapy
AU - Routy, Jean Pierre
AU - Boulassel, Mohamed Rachid
AU - Yassine-Diab, Bader
AU - Nicolette, Charles
AU - Healey, Don
AU - Jain, Renu
AU - Landry, Claire
AU - Yegorov, Oleg
AU - Tcherepanova, Irina
AU - Monesmith, Tamara
AU - Finke, Lothar
AU - Sékaly, Rafick Pierre
N1 - Funding Information:
This project has been funded in part with Federal funds from the National Institute of Allergy and Infectious Diseases , National Institutes of Health , Department of Health and Human Services , under Contract No. N01-AI-60019 and by CANVAC ( HIV-001 ) and the Canadian trials Network (CTN) Study No. 229 . Argos provided funding for statistical support, study monitoring, data management, and medical writing support. Statistical support was provided by Cemal Unal, PhD. Medical writing support was provided by Patrice Ferriola, PhD.
Funding Information:
We thank the study site personnel including Pierrette Bouchard, Mario Legault, and Marwan Samia at the clinical site, Christine Colven and Esther Villiard at Argos Therapeutics Inc., Tom Baumgartner at the University of Montreal, Quebec, Canada for providing support in the conduct of the immune assays and Dominic Gagnon for FACS data analysis at the National Immune Monitoring Laboratory. J-P Routy, is a clinician-scientist supported by Fonds de la recherche en santé du Québec (FRSQ). R-P Sekaly is the Canada Research Chair in Human Immunology.
PY - 2010/2
Y1 - 2010/2
N2 - 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.
AB - 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.
KW - Acquired immunodeficiency syndrome
KW - Dendritic cells
KW - HIV
KW - Immunotherapy
KW - Vaccine
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U2 - 10.1016/j.clim.2009.09.009
DO - 10.1016/j.clim.2009.09.009
M3 - Article
C2 - 19889582
AN - SCOPUS:73549125003
SN - 1521-6616
VL - 134
SP - 140
EP - 147
JO - Clinical Immunology
JF - Clinical Immunology
IS - 2
ER -
