Immunologic activity and safety of autologous HIV RNA-electroporated dendritic cells in HIV-1 infected patients receiving antiretroviral therapy

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2010-02, Vol.134 (2), p.140-147
• Main Authors: Routy, Jean-Pierre, Boulassel, Mohamed-Rachid, Yassine-Diab, Bader, Nicolette, Charles, Healey, Don, Jain, Renu, Landry, Claire, Yegorov, Oleg, Tcherepanova, Irina, Monesmith, Tamara, Finke, Lothar, Sékaly, Rafick-Pierre
• Format: Article
• Language: English
• Subjects: Acquired immunodeficiency syndrome; Adult; Allergy and Immunology; Anti-Retroviral Agents - therapeutic use; Autoimmunity; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Cell Count; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - transplantation; Electroporation; Fundamental and applied biological sciences. Psychology; Fundamental immunology; gag Gene Products, Human Immunodeficiency Virus - immunology; HIV; HIV - immunology; HIV Infections - immunology; HIV Infections - therapy; Human immunodeficiency virus 1; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Immunotherapy; Immunotherapy - methods; Infectious diseases; Male; Medical sciences; Middle Aged; nef Gene Products, Human Immunodeficiency Virus - immunology; Pilot Projects; rev Gene Products, Human Immunodeficiency Virus - immunology; RNA, Viral - immunology; Vaccine; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; vpr Gene Products, Human Immunodeficiency Virus - immunology
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2009.09.009

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.