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The Journal of Immunology, 2004, 173: 4882-4888.
Copyright © 2004 by The American Association of Immunologists

Regression of Established Liver Tumor Induced by Monoepitopic Peptide-Based Immunotherapy1

Elodie Belnoue2,*, Catherine Guettier{dagger}, Michèle Kayibanda*, Solène Le Rond*, Anne-Marie Crain-Denoyelle*, Carmen Marchiol*, Marianne Ziol{ddagger}, Didier Fradelizi*, Laurent Rénia* and Mireille Viguier3,*

* Département d’Immunologie, Laboratoire Associé 11 du Comité de Paris de la Ligue Nationale contre le Cancer, 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, Paris, France; {dagger} Laboratoire d’Anatomie Pathologique, Hôpital Paul Brousse, Villejuif, France; {ddagger} Service d’Anatomie Pathologique, Hôpital Jean Verdier, Bondy, France; and {ddagger}UPRES EA3406, UFR SMBH, Bobigny, France

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.







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