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

Jean Pierre Routy, Mohamed Rachid Boulassel, Bader Yassine-Diab, Charles Nicolette, Don Healey, Renu Jain, Claire Landry, Oleg Yegorov, Irina Tcherepanova, Tamara Monesmith, Lothar Finke, Rafick Pierre Sékaly

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64 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)140-147
Number of pages8
JournalClinical Immunology
Volume134
Issue number2
DOIs
Publication statusPublished - Feb 2010

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Keywords

  • Acquired immunodeficiency syndrome
  • Dendritic cells
  • HIV
  • Immunotherapy
  • Vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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