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

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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https://hal-pasteur.archives-ouvertes.fr/pasteur-00365813
Contributor : Mireille Gau <>
Submitted on : Wednesday, March 4, 2009 - 4:19:58 PM
Last modification on : Wednesday, August 19, 2020 - 11:16:58 AM

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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, Springer Verlag, 2008, 57 (8), pp.1161-71. ⟨10.1007/s00262-007-0448-3⟩. ⟨pasteur-00365813⟩

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