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

Immunotherapy. 2019 Nov;11(16):1399-1407. doi: 10.2217/imt-2019-0081. Epub 2019 Oct 14.

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.

Keywords: adoptive T-cell therapy; apoptosis; aspartate-β-hydroxylase; dendritic cells; hepatocellular carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / immunology
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / immunology*
  • Carcinoma, Hepatocellular / enzymology
  • Carcinoma, Hepatocellular / immunology
  • Carcinoma, Hepatocellular / therapy*
  • Cell Line, Tumor
  • Dendritic Cells / immunology*
  • Female
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Liver Neoplasms / enzymology
  • Liver Neoplasms / immunology
  • Liver Neoplasms / therapy*
  • Mice, Inbred C57BL
  • Mice, Nude
  • Mixed Function Oxygenases / antagonists & inhibitors
  • Mixed Function Oxygenases / immunology
  • Mixed Function Oxygenases / metabolism*
  • T-Lymphocytes / immunology
  • Xenograft Model Antitumor Assays / methods

Substances

  • Cancer Vaccines
  • Mixed Function Oxygenases
  • aspartic acid 2-oxoglutarate-dependent dioxygenase