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Delivery of mengovirus-derived RNA replicons into tumoural liver enhances the anti-tumour efficacy of a peripheral peptide-based vaccine

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Abstract

Hepatocellular carcinoma is a deadly cancer with growing incidence for which immunotherapy is one of the most promising therapeutic approach. Peptide-based vaccines designed to induce strong, sustained CD8+ T cell responses are effective in animal models and cancer patients. We demonstrated the efficacy of curative peptide-based immunisation against a unique epitope of SV40 tumour antigen, through the induction of a strong CD8+ T cell-specific response, in our liver tumour model. However, as in human clinical trials, most tumour antigen epitopes did not induce a therapeutic effect, despite inducing strong CD8+ T cell responses. We therefore modified the tumour environment to enhance peptide-based vaccine efficacy by delivering mengovirus (MV)-derived RNA autoreplicating sequences (MV-RNA replicons) into the liver. The injection of replication-competent RNA replicons into the liver converted partial tumour regression into tumour eradication, whereas non-replicating RNA had no such effect. Replicating RNA replicon injection induced local recruitment of innate immunity effectors (NK and NKT) to the tumour and did not affect specific CD8+ T cell populations or other myelolymphoid subsets. The local delivery of such RNA replicons into tumour stroma is therefore a promising strategy complementary to the use of peripheral peptide-based vaccines for treating liver tumours.

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Abbreviations

rMΔBB-GFP :

Mengovirus-derived RNA replicons expressing GFP or NP (rMΔBB-NP)

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Acknowledgments

This work was supported by a grant from Comité de Paris de La Ligue Contre le Cancer (75/2-LA/11) and from Axe 3 du Cancéropole Ile De France.

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Authors and Affiliations

  1. Institut Cochin, Département Endocrinologie-Métabolisme et Cancer (EMC), Institut National de la Santé et de la Recherche Médicale INSERM U567, 24, rue du Faubourg Saint-Jacques, 75014, Paris, France

    Jean-Pierre Couty, Anne-Marie Crain, Marilyne Labasque, Carmen Marchiol, Didier Fradelizi & Mireille Viguier

  2. Centre National de la Recherche Scientifique, CNRS UMR 8104, 24, rue du Faubourg Saint-Jacques, 75014, Paris, France

    Jean-Pierre Couty, Anne-Marie Crain, Marilyne Labasque, Carmen Marchiol, Didier Fradelizi & Mireille Viguier

  3. Université Paris-Descartes, Bâtiment Faculté, 24, rue du Faubourg Saint-Jacques, 75014, Paris, France

    Jean-Pierre Couty, Anne-Marie Crain, Marilyne Labasque, Carmen Marchiol, Didier Fradelizi & Mireille Viguier

  4. Université Paris Diderot, 2, place Jussieu, 75251, Paris Cedex 05, France

    Jean-Pierre Couty, Anne-Marie Crain, Marilyne Labasque, Sarah Boudaly & Mireille Viguier

  5. Institut Pasteur, Unité de Génétique Moléculaire des Virus Respiratoires, Unité de Recherche Associée URA 1966, Centre National de la Recherche Scientifique, CNRS, 25, rue du Docteur Roux, 75724, Paris Cedex 15, France

    Sylvie Gerbaud, Marco Vignuzzi, Sylvie van der Werf & Nicolas Escriou

  6. Laboratoire d’Immunologie Cellulaire et Immunopathologie de l’Ecole Pratique des Hautes Etudes, Institut Universitaire d’Hématologie, Unité Mixte de Recherche UMR 7151, Centre National de la Recherche Scientifique, CNRS, Hôpital Saint-Louis, 75010, Paris, France

    Sarah Boudaly

  7. Centre Hépatobiliaire, laboratoire d’Anatomie Pathologique, Hôpital Paul Brousse, 14, avenue Paul Vaillant Couturier, 94804, Villejuif, France

    Catherine Guettier

  8. Université Paris Diderot, Laboratoire associé, 2 Place Jussieu, 75251, Paris Cedex 05, France

    Sylvie Gerbaud, Marco Vignuzzi, Sylvie van der Werf & Nicolas Escriou

Authors
  1. Jean-Pierre Couty
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  2. Anne-Marie Crain
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  3. Sylvie Gerbaud
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  4. Marilyne Labasque
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  5. Carmen Marchiol
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  6. Didier Fradelizi
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  7. Sarah Boudaly
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  8. Catherine Guettier
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  9. Marco Vignuzzi
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  10. Sylvie van der Werf
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  11. Nicolas Escriou
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  12. Mireille Viguier
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Corresponding author

Correspondence to Mireille Viguier.

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Jean-Pierre Couty and Anne-Marie Crain contributed equally to this work.

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Couty, JP., Crain, AM., Gerbaud, S. et al. Delivery of mengovirus-derived RNA replicons into tumoural liver enhances the anti-tumour efficacy of a peripheral peptide-based vaccine. Cancer Immunol Immunother 57, 1161–1171 (2008). https://doi.org/10.1007/s00262-007-0448-3

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  • DOI: https://doi.org/10.1007/s00262-007-0448-3

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