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Anti-tumor Efficacy of a Hepatocellular Carcinoma Vaccine Based on Dendritic Cells Combined with Tumor-derived Autophagosomes in Murine Models

  • Su, Shu (Cancer Research and Biotherapy Center, the Affiliated Nanjing Second Hospital, Medical School of Southeast University) ;
  • Zhou, Hao (Department of Microbiology and Immunology, Medical School of Southeast University) ;
  • Xue, Meng (Department of Microbiology and Immunology, Medical School of Southeast University) ;
  • Liu, Jing-Yu (Department of Microbiology and Immunology, Medical School of Southeast University) ;
  • Ding, Lei (Department of Microbiology and Immunology, Medical School of Southeast University) ;
  • Cao, Meng (Department of Microbiology and Immunology, Medical School of Southeast University) ;
  • Zhou, Zhen-Xian (Cancer Research and Biotherapy Center, the Affiliated Nanjing Second Hospital, Medical School of Southeast University) ;
  • Hu, Hong-Min (Cancer Research and Biotherapy Center, the Affiliated Nanjing Second Hospital, Medical School of Southeast University) ;
  • Wang, Li-Xin (Cancer Research and Biotherapy Center, the Affiliated Nanjing Second Hospital, Medical School of Southeast University)
  • Published : 2013.05.30

Abstract

The majority of hepatocellular carcinoma (HCC) patients have a poor prognosis with current therapies, and new approaches are urgently needed. We have developed a novel therapeutic cancer vaccine platform based on tumor cell derived autophagosomes (DRibbles) for cancer immunotherapy. We here evaluated the effectiveness of DRibbles-pulsed dendritic cell (DC) immunization to induce anti-tumor immunity in BALB/c mouse HCC and humanized HCC mouse models generated by transplantation of human HCC cells (HepG2) into BALB/c-nu mice. DRibbles were enriched from H22 or BNL cells, BALB/c-derived HCC cell lines, by inducing autophagy and blocking protein degradation. DRibbles-pulsed DC immunization induced a specific T cell response against HCC and resulted in significant inhibition of tumor growth compared to mice treated with DCs alone. Antitumor efficacy of the DCs-DRibbles vaccine was also demonstrated in a humanized HCC mouse model. The results indicated that HCC/DRibbles-pulsed DCs immunotherapy might be useful for suppressing the growth of residual tumors after primary therapy of human HCC.

Keywords

Hepatocellular carcinoma;dendritic cells;autophagy;immunotherapy;tumor antigen;cross-presentation

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