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

Jean-Pierre Couty (1, 2, 3, 4) , Anne-Marie Crain (1, 2, 3, 4) , Sylvie Gerbaud (4, 5) , Marilyne Labasque (1, 2, 3, 4) , Carmen Marchiol (1, 2, 3) , Didier Fradelizi (1, 2, 3) , Sarah Boudaly (4, 6) , Catherine Guettier (7) , Marco Vignuzzi (4, 5) , Sylvie van Der Werf (4, 5) , Nicolas Escriou (4, 5) , Mireille Viguier (1, 2, 3, 4)

1 UMR_S567 / UMR 8104 - Institut Cochin
2 IC UM3 (UMR 8104 / U1016) - Institut Cochin
3 UPD5 - Université Paris Descartes - Paris 5
4 UPD7 - Université Paris Diderot - Paris 7
5 Génétique Moléculaire des Virus Respiratoires
6 Pathologie cellulaire : aspects moléculaires et viraux / Pathologie et Virologie Moléculaire
7 Laboratoire d'Anatomie Pathologique

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.

Jean-Pierre Couty, Anne-Marie Crain, Sylvie Gerbaud, Marilyne Labasque, Carmen Marchiol, et al.. Delivery of mengovirus-derived RNA replicons into tumoural liver enhances the anti-tumour efficacy of a peripheral peptide-based vaccine.. Cancer Immunology, Immunotherapy, 2008, 57 (8), pp.1161-71. ⟨10.1007/s00262-007-0448-3⟩. ⟨pasteur-00365813⟩