Regression of established liver tumor induced by monoepitopic peptide-based immunotherapy.
Most types of cancer are difficult to eradicate, and some, like hepatocellular carcinoma, are almost always fatal. Among various interventions to improve the survival of patients with cancer, immunotherapy seems to hold some promises. However, it requires relevant animal models for preclinical development. In this study we report a new and relevant experimental model where liver tumors grow inside a nontumoral parenchyma of adult mice. This model is based on the intrasplenic injection in syngeneic recipient mice of hepatocytes from transgenic mice expressing SV40 large T oncogene specifically in the liver. Using this model where no apparent spontaneous cellular immune response was observed, immunization using a single injection of monoepitopic SV40 T Ag short peptide was sufficient to provoke liver tumor destruction, leading rapidly to complete remission. Tumor regression was associated with the induction of a long-lasting CD8+ T cell response, observed not only in the spleen but also, more importantly, in the tumoral liver. These results show the efficacy of peptide immunotherapy in the treatment of liver cancer.
Département d'Immunologie, Institut Cochin, Institut National de la Santé et de la Recherche Médicale, Unité 567, Centre National de la Recherche Scientifique, Université René Descartes, Hôpital Cochin, France.
Elodie
E
Belnoue
Catherine
C
Guettier
Michèle
M
Kayibanda
Solène
S
Le Rond
Anne-Marie
AM
Crain-Denoyelle
Carmen
C
Marchiol
Marianne
M
Ziol
Didier
D
Fradelizi
Laurent
L
Rénia
Mireille
M
Viguier
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement; D007114:Immunization; D007167:Immunotherapy; D007371:Interferon-gamma / Q000096:biosynthesis; D008114:Liver Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology*
D000952:Antigens, Polyomavirus Transforming; D010446:Peptide Fragments; D007371:Interferon-gamma