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© Research
Publication : Cancer immunology, immunotherapy : CII

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Cancer immunology, immunotherapy : CII - 07 Feb 2008

Couty JP, Crain AM, Gerbaud S, Labasque M, Marchiol C, Fradelizi D, Boudaly S, Guettier C, Vignuzzi M, van der Werf S, Escriou N, Viguier M

Link to Pubmed [PMID] – 18256833

Cancer Immunol. Immunother. 2008 Aug;57(8):1161-71

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.

http://www.ncbi.nlm.nih.gov/pubmed/18256833