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Table 1 Biological effects of DCs-based vaccines in HCC: representative in vitro and in vivo investigations

From: From bench to bed: the tumor immune microenvironment and current immunotherapeutic strategies for hepatocellular carcinoma

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]

  1. Notes: TAA tumor-associated antigens, MAGE-1 melanoma-associated antigen 1, GPC-3 glypican-3, IL-12 interleukin-12, AFP a-fetoprotein, TEXs tumor cell–derived exosomes, TGF-β transforming growth factor-β, TME tumor microenvironment, IFN-γ interferon-γ, DEXs dendritic cell-derived exosomes, CTLs cytotoxic T lymphocytes, Tregs regulatory T cells