Immunologic activity and safety of autologous HIV RNA-electroporated dendritic cells in HIV-1 infected patients receiving antiretroviral therapy.
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.
Routy
Jean-Pierre
JP
Immunodeficiency Service and Division of Hematology, McGill University Health Centre, McGill University, Montreal, Qc, Canada. RoutyJP@muhchem.mcgill.ca
Boulassel
Mohamed-Rachid
MR
Yassine-Diab
Bader
B
Nicolette
Charles
C
Healey
Don
D
Jain
Renu
R
Landry
Claire
C
Yegorov
Oleg
O
Tcherepanova
Irina
I
Monesmith
Tamara
T
Finke
Lothar
L
Sékaly
Rafick-Pierre
RP
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
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