AFP-specific immunotherapy impairs growth of autochthonous hepatocellular carcinoma in mice
| Autor: | Lucile Tran, Bruno Pitard, Jean-Pierre Couty, Isabelle Archambeaud, Bruno Turlin, Vanessa Gauttier, Benoit Barteau, Nicolas Ferry, Sophie Conchon, Jeannette Cany, Georges Vassaux |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Pathology medicine.medical_specialty medicine.medical_treatment Genetic Vectors Context (language use) CD8-Positive T-Lymphocytes Cancer Vaccines DNA vaccination Mice Liver Neoplasms Experimental MHC class I Vaccines DNA medicine Animals Diethylnitrosamine Mice Inbred C3H Hepatology biology business.industry H-2 Antigens Immunotherapy Active Cancer Immunotherapy medicine.disease digestive system diseases Mice Inbred C57BL Hepatocellular carcinoma biology.protein Cancer research Female alpha-Fetoproteins Alpha-fetoprotein business Adjuvant |
| Zdroj: | Journal of Hepatology. 54:115-121 |
| ISSN: | 0168-8278 |
| DOI: | 10.1016/j.jhep.2010.06.027 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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