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.
Cany
Jeannette
J
INSERM U948, Biothérapies Hépatiques, Nantes, France.
Barteau
Benoît
B
Tran
Lucile
L
Gauttier
Vanessa
V
Archambeaud
Isabelle
I
Couty
Jean-Pierre
JP
Turlin
Bruno
B
Pitard
Bruno
B
Vassaux
Georges
G
Ferry
Nicolas
N
Conchon
Sophie
S
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