AFP-specific immunotherapy impairs growth of autochthonous hepatocellular carcinoma in mice

J Hepatol. 2011 Jan;54(1):115-21. doi: 10.1016/j.jhep.2010.06.027. Epub 2010 Aug 26.


Background and aims: In this study, we have assessed the potential of antigen-specific immunotherapy against hepatocellular carcinoma (HCC) in conditions of low tumour burden, in an autochthonous HCC model.

Methods: Diethylnitrosamine (DEN) injected into infant mice results in the development of multi-nodular HCC in which alpha-fetoprotein (AFP) is re-expressed. DEN-injected animals received an antigen-specific immunization with a synthetic vector consisting of a low dose of AFP-encoding plasmid formulated with the amphiphilic block copolymer 704 (DNAmAFP/704). Animals were treated at 4 and 5 months, before macroscopic nodules were detected, and were sacrificed at 8 months. The tumour burden, as well as liver histology, was assessed. AFP and MHC class I molecule expression in the nodules were monitored by qRT-PCR.

Results: The AFP-specific immunotherapy led to a significant (65%) reduction in tumour size. The reduced expression of AFP and MHC class I molecules was measured in the remaining nodules taken from the DNAmAFP/704-treated group.

Conclusions: This is the first study demonstrating the relevance of antigen-specific immunotherapy in an autochthonous HCC model. In this context, we validated the use of an anti-tumour immunotherapy based on vaccination with nanoparticles consisting of low dose antigen-encoding DNA formulated with a block copolymer. Our results demonstrate the potential of this strategy as adjuvant immunotherapy to reduce the recurrence risk after local treatment of HCC patients.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / pharmacology
  • Diethylnitrosamine / toxicity
  • Female
  • Genetic Vectors
  • H-2 Antigens / metabolism
  • Immunotherapy, Active*
  • Liver Neoplasms, Experimental / chemically induced
  • Liver Neoplasms, Experimental / immunology
  • Liver Neoplasms, Experimental / pathology
  • Liver Neoplasms, Experimental / therapy*
  • Male
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Vaccines, DNA / pharmacology
  • alpha-Fetoproteins / antagonists & inhibitors*
  • alpha-Fetoproteins / genetics
  • alpha-Fetoproteins / immunology*


  • Cancer Vaccines
  • H-2 Antigens
  • H-2K(K) antigen
  • H-2Kb protein, mouse
  • Vaccines, DNA
  • alpha-Fetoproteins
  • Diethylnitrosamine