Delivery of mengovirus-derived RNA replicons into tumoural liver enhances the anti-tumour efficacy of a peripheral peptide-based vaccine.
In: ISSN: 0340-7004, 2008
academicJournal
Zugriff:
International audience ; 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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Delivery of mengovirus-derived RNA replicons into tumoural liver enhances the anti-tumour efficacy of a peripheral peptide-based vaccine.
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Autor/in / Beteiligte Person: | Couty, Jean-Pierre ; Crain, Anne-Marie ; Gerbaud, Sylvie ; Labasque, Marilyne ; Marchiol, Carmen ; Fradelizi, Didier ; Boudaly, Sarah ; Guettier, Catherine ; Vignuzzi, Marco ; van Der Werf, Sylvie ; Escriou, Nicolas ; Viguier, Mireille ; Institut Cochin (UMR_S567 / UMR 8104) ; Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) ; Institut Cochin (IC UM3 (UMR 8104 / U1016)) ; Université Paris Descartes - Paris 5 (UPD5) ; Université Paris Diderot - Paris 7 (UPD7) ; Génétique Moléculaire des Virus Respiratoires ; Institut Pasteur Paris (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS) ; Pathologie cellulaire : aspects moléculaires et viraux / Pathologie et Virologie Moléculaire ; Institut Universitaire d'Hématologie (IUH) ; Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal Paris ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS) ; Laboratoire d'Anatomie Pathologique ; Hôpital Paul Brousse |
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Zeitschrift: | ISSN: 0340-7004, 2008 |
Veröffentlichung: | HAL CCSD ; Springer Verlag, 2008 |
Medientyp: | academicJournal |
DOI: | 10.1007/s00262-007-0448-3 |
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