alpha-fetoprotein and interleukin-18 gene-modified dendritic cells effectively stimulate specific type-1 CD4- and CD8-mediated T-Cell response from hepatocellular carcinoma patients in Vitro.

Abstract:

:The T-helper 1 (Th1) immune reaction is most important in dendritic cell (DC)-based immunotherapy. Interleukin (IL)-18, a Th1-biasing cytokine, plays a pivotal role in inducing cytotoxic T lymphocyte (CTL) responses. In this study, we analyzed whether dendritic cells (DCs) from patients with hepatocellular carcinoma (HCC) can be transduced with the IL-18 gene and/or alpha-fetoprotein (AFP) gene, and we examined whether vaccinations using these genetically engineered DC can induce stronger therapeutic antitumor immunity. The results showed that DC transfected with AdIL-18/AFP can expressed IL-18 and AFP by reverse transcriptase-polymerase chain reaction and enzyme-linked immunoassay. Compared with those before transfection, the expressions of membrane molecules were increased dramatically. Specific T cells generated by DC transfected with AdIL-18/AFP recognized HLA-matched HepG2 cell lines specifically. Most importantly, The cytotoxic activity of CTLs against HepG2 with DC expressing AFP(AFP-DC) was significantly augmented by co-transduction with the IL-18 gene. Administration with such vaccine also significantly increased the production of interleukin-12p70 and interferon-gamma. These results indicate that a vaccination therapy using DC co-transduced with the TAA gene and IL-18 genes is effective strategy for immunotherapy in terms of the activation of DCs, CD4+ T, cells and CD8+ T cells, and may be useful in the clinical application of a cancer vaccine therapy.

journal_name

Hum Immunol

journal_title

Human immunology

authors

Cao DY,Yang JY,Dou KF,Ma LY,Teng ZH

doi

10.1016/j.humimm.2007.01.008

subject

Has Abstract

pub_date

2007-05-01 00:00:00

pages

334-41

issue

5

eissn

0198-8859

issn

1879-1166

pii

S0198-8859(07)00020-1

journal_volume

68

pub_type

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