title: Immunologic activity and safety of autologous HIV RNA-electroporated dendritic cells in HIV-1 infected patients receiving antiretroviral therapy.
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.
authors.affiliation: Immunodeficiency Service and Division of Hematology, McGill University Health Centre, McGill University, Montreal, Qc, Canada. RoutyJP@muhchem.mcgill.ca
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Routy
authors.forename: Mohamed-Rachid
authors.initials: MR
authors.lastname: Boulassel
authors.forename: Bader
authors.initials: B
authors.lastname: Yassine-Diab
authors.forename: Charles
authors.initials: C
authors.lastname: Nicolette
authors.forename: Don
authors.initials: D
authors.lastname: Healey
authors.forename: Renu
authors.initials: R
authors.lastname: Jain
authors.forename: Claire
authors.initials: C
authors.lastname: Landry
authors.forename: Oleg
authors.initials: O
authors.lastname: Yegorov
authors.forename: Irina
authors.initials: I
authors.lastname: Tcherepanova
authors.forename: Tamara
authors.initials: T
authors.lastname: Monesmith
authors.forename: Lothar
authors.initials: L
authors.lastname: Finke
authors.forename: Rafick-Pierre
authors.initials: RP
authors.lastname: Sékaly
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002452:Cell Count; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation*; D018274:Electroporation; D006678:HIV / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012367:RNA, Viral / Q000276:immunology*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000276:immunology; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000276:immunology; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D044966:Anti-Retroviral Agents; D012367:RNA, Viral; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus; D054321:rev Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus