Agents | Descriptions | Trial category | Biological effects or clinical results | References |
---|---|---|---|---|
AFP and interleukin 18 engineered DCs (AFP/IL-18-DCs) | DCs co-transduced with the AFP gene and IL-18 | In vitro studies | • Significantly increase the production of IFN-γ • Promote CD4+ T cells proliferation; elevate CTLs activity against AFP-expressing HCC cells | [97] |
DCs pulsed with NY-ESO-1 | DCs pulsed with the recombinant NY-ESO-1 protein | In vitro studies | • Be more effective in stimulating T cell proliferation compared with immature DCs | [98] |
IL-12 engineered DCs (IL-12-DCs) | Endogenous IL-12-expression by adenoviral gene transfer effectively enhances immunostimulation of DC | Translational trials with murine models | • Induce a sufficient Th1 TME allowing the recruitment of Teff to enhance anti-tumor immunity • Improve dendritic cells (DCs)-based immunotherapy of HCC | [99] |
CD40 Ligand-Expressing DCs | Transduction of TAA-pulsed DCs with CD40L-encoding adenovirus (Ad-CD40L) | Translational trials with mice models | • Promote DC immunostimulation with up-regulation of CD80/CD86 and IL-12 expression • Increase tumor infiltration with CD4+, CD8+ T cells and NK cells • Elevate IFN-γ release and CTLs cytotoxicity | [100] |
TEXs pulsed DCs | Tumor cell derived exosomes (TEXs)-pulsed DCs | In vitro and in vivo orthotopic HCC mice models | • Increase numbers of T lymphocytes infiltration, elevate IFN-γ production; decrease IL-10, TGF-β in tumor sites • Elicit a stronger immune response than cell lysates in vitro and in vivo | [95] |
A new form vaccine: DCs-DEXs | Exosomes derived from AFP- expressing DCs | Translational investigation in mouse models | • A cell-free vaccine option for HCC immunotherapy • Decrease Tregs infiltration, IL-10, TGF-β in tumor sites • Reshape the TME in HCC | [96] |
TAAs pulsed DCs vaccine | α-fetoprotein, glypican-3 and MAGE-1 recombinant fusion proteins pulsed DCs | A prospective phase I/II clinical study in 5 HCC patients | • Result: safe and well-tolerated • Over 95% of DCs demonstrated highly expressed MHC class I (HLA-ABC), MHC class II (HLA-DR), and costimulatory molecules (CD86, CD80, and CD40) • Induce Th1 immune responses with highly produced IL-12, IFN-γ • Trigger stronger CTLs responses | [101] |
TAAs pulsed DCs vaccine | α-fetoprotein, glypican-3 and MAGE-1 recombinant fusion proteins pulsed DCs | A prospective phase I/II clinical study in 12 HCC patients | • Result: safe and well-tolerated • 1-, 2-, and 5-year cumulative RFS rates were improved | [102] |
DCs pulsed with tumor cell lysate | Mature autologous DCs pulsed exvivo with HepG2 lysate | A phase II clinical trial with 35 patients with advanced HCC | • Result: safe and well-tolerated • MS: 168 days; 6-month survival rate: 33%; 1-year survival rate 11% • Induce stronger T cell responses and IFN-γ release | [103] |
DCs pulsed with tumor cell lysate | Mature autologous DCs pulsed ex vivo with HepG2 lysate | A clinical trial with 2 groups: Group1: 15 advanced HCC patients received DCs vaccination Group2: control group | • Result: safe and well-tolerated • CD8+ T cells and serum IFN-γ were elevated after DCs injection • Partial radiological response: 13.3%; stable course: 60%; and 26.7% showed progressive disease and died at 4 months post-injection | [104] |
DCs pulsed with AFP | AFP peptides pulsed onto autologous DCs | A phase I/II clinical trial in which HLA-A*0201 patients with AFP-positive HCC, 10 patients received DCs vaccination | • 6 of 10 subjects increased IFN-γ producing AFP-specific T cell responses | [105] |