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

• DOI: 10.1016/j.jhep.2010.06.027
• Publication Date: 2010-08-27T09:31:17Z
• Authors: Jeannette Cany; Benoît Barteau; Lucile Tran; Vanessa Gauttier; Isabelle Archambeaud; Jean-Pierre Couty; Bruno Turlin; Bruno Pitard; Georges Vassaux; Nicolas Ferry; Sophie Conchon
• Keywords: Male; Mice, Inbred C3H; Genetic Vectors; H-2 Antigens; Immunotherapy, Active; CD8-Positive T-Lymphocytes; Cancer Vaccines; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Liver Neoplasms, Experimental; 0302 clinical medicine; Vaccines, DNA; Animals; Diethylnitrosamine; Female; alpha-Fetoproteins

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.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.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.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.