Dendritic cell-based vaccine targeting aspartate-β-hydroxylas represents a promising therapeutic strategy for HCC

Abstract

Background: Dendritic cells (DCs)-mediated immunotherapy has been considered as a promising antitumor method. Aspartate-β-hydroxylase ( AAH) is a potential immunotherapeutic target for hepatocellular carcinoma (HCC). Materials & methods: C57BL/6 mice were immunized by AAH-DCs vaccine constructed ex vivo. Killing tumor cells effect of active T cells induced by AAH-DCs vaccine on HCC cells were measured in vitro and vivo. The underlying mechanism was preliminarily investigated. Results: T cells response when activated by AAH-DCs vaccine showed a significant inhibition effect on HCC cells in vitro and in tumor-bearing mice models when compared with controls. Additionally, compared with the control group, increased expressions of Caspase8, Caspase 3 and Bax, and declined expression of Bcl-2 were observed in AAH-DCs vaccine group. Conclusion: AAH-DCs vaccine could stimulate T cell responses against HCC, which was possibly achieved via pro-apoptosis mechanism.

Dendritic-Cell-Vaccine-Based Immunotherapy for Hepatocellular Carcinoma: Clinical Trials and Recent Preclinical Studies

“…The results showed that CD90-positive irradiated HepG2 cell-fused DC vaccine induced stronger IFN-γ-producing CTL-mediated cytotoxicity against CD90-positive HepG2 cell line in vitro and exhibited better efficacy in suppressing tumor growth in an ectopic xenograft immunocompromised BALB/c mouse model of non-CD90-sorted HepG2 cell line than non-CD90-sorted irradiated HepG2 cell-fused DC vaccine. Another study performed by Zhou et al evaluated the efficacy of a mature-DC vaccine, which was transfected with adenoviral vector DNA containing a gene encoding the HCC tumor marker aspartate-β-hydroxylase (AAH), in treating HCC [ 55 ]. The results showed that AAH DNA-transfected DC vaccine induced stronger IFN-γ-producing CTL-mediated cytotoxicity against human HCC cell line SMMC-7721 in vitro and exhibited better efficacy in suppressing tumor growth in an ectopic xenograft immunocompromised BALB/c mouse model than non-AAH DNA-transfected DC vaccine.…”