1. α-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
- Author
-
Cao, Da-Yong, Yang, Jing-Yue, Dou, Ke-Feng, Ma, Long-yang, and Teng, Zeng-Hui
- Subjects
- *
CANCER treatment , *CANCER patients , *DENDRITIC cells , *LYMPHOID tissue - Abstract
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 α-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-γ. 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. [Copyright &y& Elsevier]
- Published
- 2007
- Full Text
- View/download PDF