AFP-specific immunotherapy impairs growth of autochthonous hepatocellular carcinoma in mice.
OBJECTIVE
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.
INSERM U948, Biothérapies Hépatiques, Nantes, France.
Jeannette
J
Cany
Benoît
B
Barteau
Lucile
L
Tran
Vanessa
V
Gauttier
Isabelle
I
Archambeaud
Jean-Pierre
JP
Couty
Bruno
B
Turlin
Bruno
B
Pitard
Georges
G
Vassaux
Nicolas
N
Ferry
Sophie
S
Conchon
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000494:pharmacology; D004052:Diethylnitrosamine / Q000633:toxicity; D005260:Female; D005822:Genetic Vectors; D006183:H-2 Antigens / Q000378:metabolism; D016233:Immunotherapy, Active; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D019444:Vaccines, DNA / Q000494:pharmacology; D000509:alpha-Fetoproteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology*
D019496:Cancer Vaccines; D006183:H-2 Antigens; C024755:H-2K(K) antigen; C032876:H-2Kb protein, mouse; D019444:Vaccines, DNA; D000509:alpha-Fetoproteins; D004052:Diethylnitrosamine