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

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

Authors :
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]
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)
Source :
Cancer Immunology, Immunotherapy, Cancer Immunology, Immunotherapy, Springer Verlag, 2008, 57 (8), pp.1161-71. ⟨10.1007/s00262-007-0448-3⟩, Cancer Immunology, Immunotherapy, 2008, 57 (8), pp.1161-71. ⟨10.1007/s00262-007-0448-3⟩, Cancer Immunology and Immunotherapy, Cancer Immunology and Immunotherapy, 2008, 57 (8), pp.1161-71. 〈10.1007/s00262-007-0448-3〉
Publication Year :
2008
Publisher :
HAL CCSD, 2008.

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.

Subjects

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

Details

Language :
English
ISSN :
03407004 and 14320851
Database :
OpenAIRE
Journal :
Cancer Immunology, Immunotherapy, Cancer Immunology, Immunotherapy, Springer Verlag, 2008, 57 (8), pp.1161-71. ⟨10.1007/s00262-007-0448-3⟩, Cancer Immunology, Immunotherapy, 2008, 57 (8), pp.1161-71. ⟨10.1007/s00262-007-0448-3⟩, Cancer Immunology and Immunotherapy, Cancer Immunology and Immunotherapy, 2008, 57 (8), pp.1161-71. 〈10.1007/s00262-007-0448-3〉
Accession number :
edsair.doi.dedup.....89120fc82a737f852c1cc9cd5015a0d5
Full Text :
https://doi.org/10.1007/s00262-007-0448-3⟩