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/mm3 | <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/mm3 | <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/mm3 | <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/mm3 | ≤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/mm3 | <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 |