1. Delivery of mengovirus-derived RNA replicons into tumoural liver enhances the anti-tumour efficacy of a peripheral peptide-based vaccine
- Author
-
Sylvie van der Werf, Mireille Viguier, Carmen Marchiol, Didier Fradelizi, Anne-Marie Crain, Jean-Pierre Couty, Sarah Boudaly, Marilyne Labasque, Marco Vignuzzi, Catherine Guettier, Nicolas Escriou, Sylvie Gerbaud, Institut Cochin (UMR_S567 / UMR 8104), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Université Paris Diderot - Paris 7 (UPD7), Génétique Moléculaire des Virus Respiratoires, Institut Pasteur [Paris]-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) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Anatomie Pathologique, Hôpital Paul Brousse, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [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), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), 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 ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ), Université Paris Diderot - Paris 7 ( UPD7 ), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'Immunologie Cellulaire et Immunopathologie de l'Ecole Pratique des Hautes Etudes, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
Male ,MESH : Prevalence ,MESH: Immunotherapy ,medicine.medical_treatment ,MESH: Flow Cytometry ,Epitope ,MESH: Cancer Vaccines ,Mice ,0302 clinical medicine ,MESH: Liver Neoplasms ,Cytotoxic T cell ,MESH: Animals ,Replicon ,MESH : Influenza A Virus, H9N2 Subtype ,MESH: Phylogeny ,MESH: Treatment Outcome ,0303 health sciences ,MESH : Peptides ,MESH: Peptides ,Liver Neoplasms ,MESH : Reverse Transcriptase Polymerase Chain Reaction ,Flow Cytometry ,MESH : Influenza in Birds ,3. Good health ,MESH : Influenza A virus ,MESH : Immunotherapy ,Oncology ,MESH: RNA, Viral ,MESH : Animal Migration ,Immunotherapy ,Carcinoma, Hepatocellular ,T cell ,Immunology ,MESH: Replicon ,03 medical and health sciences ,MESH: Species Specificity ,MESH: Animals, Wild ,MESH : Birds ,MESH: Prevalence ,Histocompatibility Antigens Class I ,Mengovirus ,RNA ,MESH : Disease Models, Animal ,Mice, Inbred C57BL ,MESH: Disease Models, Animal ,Peptides ,MESH: Female ,Cancer Research ,MESH : Liver Neoplasms ,MESH : Mengovirus ,MESH: Histocompatibility Antigens Class I ,MESH: Reverse Transcriptase Polymerase Chain Reaction ,Immunology and Allergy ,MESH : Female ,MESH: Carcinoma, Hepatocellular ,MESH : Animals, Wild ,MESH : Cloaca ,biology ,MESH : Cancer Vaccines ,MESH: Animal Migration ,medicine.anatomical_structure ,Treatment Outcome ,MESH: Birds ,MESH: Sentinel Surveillance ,RNA, Viral ,MESH : Histocompatibility Antigens Class I ,MESH : Replicon ,MESH : Carcinoma, Hepatocellular ,MESH : Sentinel Surveillance ,MESH : Flow Cytometry ,MESH : Male ,MESH: Influenza A virus ,MESH : Mice, Inbred C57BL ,MESH : Treatment Outcome ,Cancer Vaccines ,MESH: Influenza in Birds ,MESH: Mice, Inbred C57BL ,MESH : Mice ,medicine ,MESH : Species Specificity ,MESH : RNA, Viral ,Animals ,MESH : France ,MESH: Mice ,030304 developmental biology ,MESH : Phylogeny ,biology.organism_classification ,MESH: Male ,MESH: Cloaca ,MESH: Influenza A Virus, H9N2 Subtype ,MESH: France ,Disease Models, Animal ,MESH : Animals ,CD8 ,MESH: Mengovirus ,030215 immunology - Abstract
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.
- Published
- 2008
- Full Text
- View/download PDF