The Evolution of Dendritic Cell Immunotherapy against HIV-1 Infection: Improvements and Outlook

Table 1

List of DC immunotherapy clinical trials within the last ten years that utilized dendritic cells electroporated with HIV-1 mRNA and their therapeutic outcomes. Clinical trials differed by antigen loaded in dendritic cells, inclusion of an adjuvant, method of administration to the subject, required adherence to ART, and measured changes in immune responses subsequent to vaccine administration.

	Patient selection criteria			Study design				Postvaccination efficacy measures
Study	Starting CD4^+ T count	Starting viral load	Patient medical history	Autologous antigen	Method of introduction	Dose frequency	Duration of study	Effect on CTL response	Associated cytokines produced	Clinical outcome conclusions
Routy et al. [38]; AGS-004; Phase II	≥350 cells/mm^3	<200 copies of RNA/mL	ART suppressed; No coinfection with hepatitis B or C; No use of systemic steroids or hydroxyurea	Gag, Nef, Rev, and Vpr and CD40L	Intradermal	Every 4 weeks in combination with ART	≥12 weeks	CD8^+ T-cell proliferative responses were elevated at 4 and/or 8 weeks for all subjects	Not reported	Full or partial responses specific for the AGS-004; presented HIV antigens occurred in most subjects
Jacobson et al. [36]; AGS-004; Phase IIB	>450 cells/mm^3	<50 copies/mL	ART suppressed (≥3 months)	Gag, Nef, Rev, and Vpr and CD40L	Intradermal	Every 4 weeks; ART interruption at week 16 for 12 weeks	32 weeks	Increase of CD28/CD45RA^-CD8 effector memory T-cell response after 2 doses	IL-2, IFN-γ, TNF-α	No antiviral effect; Increased CTL response did not correlate with reduced viral load
Van Gulck et al. [56]; Phase I/II	>200 cells/mm^3	<50 copies/mL	ART suppressed	Gag and a chimeric Tat-Rev-Nef	Half subcutaneous, half intradermal	Every 4 weeks in combination with ART	≥18 weeks	Increase of HIV-specific CD8^+ T-cell responses	Gag-specific IFN-γ most significant	Improved antiviral response associated with Gag-specific IFN-γ response
Allard et al. [39]; NTR2198; Phase I/IIa	>500 cells/mm^3	≤50 copies/mL	ART suppressed; No coinfection with hepatitis B or C; No HIV-1 seroconversion within one year prior to study; No history of lymph node irradiation	Tat, Rev, or Nef	Half subcutaneous, half intradermal	Every 4 weeks; ART interruption at 14 weeks for ≤96 weeks	>96 weeks	Induction of Tat-, Rev-, and Nef-specific IFN-γ response	Gag-specific IFN-γ most significant	No correlation between any of the T-cell responses and the time remaining off cART was found; No considerable decrease in plasma viral load
Gandhi et al. [50]; PARC002; Pilot study	>300 cells/mm^3	<50 copies/mL	ART suppressed; No HCV antibody positivity; No history of cardiac, gastrointestinal, hepatic, renal, pancreatic, neurologic, or autoimmune disease	Gag, Nef, and neoantigen KLH	Intradermal	At weeks 0, 2, 6, and 10	48 weeks	No Gag-specific or Nef-specific IFN-γ response	Overall levels of IL-2, IFN-γ, and TNF-α inconclusive	No Gag-specific or Nef-specific IFN-γ response; Short-lived 2.5-fold increases in CD4^+ T-cell proliferative response from baseline to HIV-1 Gag and 2.3-fold increase to HIV-1 Nef