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4 results on '"MESH : Immunotherapy"'

1. Cytotoxic Dendritic Cells Generated from Cancer Patients

Author

Salem Chouaib, Pascal Foucher, Jennifer Fraszczak, Bernard Bonnotte, Denis Caillot, Sylvain Audia, Marion Ciudad, Catherine Vergely, Daniela Lakomy, Maxime Samson, Malika Trad, Julien Vinit, Emmanuel Katsanis, Laurent Lagrost, Nicolas Larmonier, Nona Janikashvili, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), IFR100 - Structure fédérative de recherche Santé-STIC, Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Cytokines et Immunologie des Tumeurs Humaines (U753), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy (IGR), University of Arizona, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés ( TRACES ), École des hautes études en sciences sociales ( EHESS ) -Université Toulouse - Jean Jaurès ( UT2J ) -Ministère de la Culture et de la Communication ( MCC ) -Institut national de recherches archéologiques préventives ( Inrap ) -Centre National de la Recherche Scientifique ( CNRS ), Cytokines et Immunologie des Tumeurs Humaines ( U753 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Steele Children's Research Center, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés (TRACES), École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Vergely, Catherine, Immunologie intégrative des tumeurs et immunothérapie des cancers (INTIM), and Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay

Subjects
Cytotoxicity, Immunologic, Lipopolysaccharides, MESH: Immunotherapy, medicine.medical_treatment, T-Lymphocytes, [SDV]Life Sciences [q-bio], MESH : Cytotoxicity, Immunologic, MESH: Flow Cytometry, MESH : Lipopolysaccharides, Lymphocyte Activation, 0302 clinical medicine, Cancer immunotherapy, Neoplasms, Immunology and Allergy, Cytotoxic T cell, MESH: Neoplasms, Cytotoxicity, MESH : Peroxynitrous Acid, MESH: Peroxynitrous Acid, 0303 health sciences, MESH: Dendritic Cells, hemic and immune systems, Flow Cytometry, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH : Immunotherapy, Immunotherapy, MESH : Flow Cytometry, Immunology, chemical and pharmacologic phenomena, Biology, Article, 03 medical and health sciences, Immune system, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Peroxynitrous Acid, medicine, Humans, MESH: Cytotoxicity, Immunologic, MESH: Lymphocyte Activation, MESH : Lymphocyte Activation, 030304 developmental biology, MESH : T-Lymphocytes, MESH: Humans, Follicular dendritic cells, [ SDV ] Life Sciences [q-bio], MESH : Humans, Cancer, Dendritic Cells, medicine.disease, MESH : Neoplasms, MESH: T-Lymphocytes, MESH : Dendritic Cells, Cancer cell, MESH: Lipopolysaccharides, 030215 immunology
Abstract

Known for years as professional APCs, dendritic cells (DCs) are also endowed with tumoricidal activity. This dual role of DC as killers and messengers may have important implications for tumor immunotherapy. However, the tumoricidal activity of DCs has mainly been investigated in animal models. Cancer cells inhibit antitumor immune responses using numerous mechanisms, including the induction of immunosuppressive/ tolerogenic DCs that have lost their ability to present Ags in an immunogenic manner. In this study, we evaluated the possibility of generating tumor killer DCs from patients with advanced-stage cancers. We demonstrate that human monocyte-derived DCs are endowed with significant cytotoxic activity against tumor cells following activation with LPS. The mechanism of DC-mediated tumor cell killing primarily involves peroxynitrites. This observed cytotoxic activity is restricted to immature DCs. Additionally, after killing, these cytotoxic DCs are able to activate tumor Ag-specific T cells. These observations may open important new perspectives for the use of autologous cytotoxic DCs in cancer immunotherapy strategies.

Published
2012
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2. Regression of high-grade cervical intraepithelial neoplasia with TG4001 targeted immunotherapy

Author

Serge Douvier, Christine Clavel, Jean Lévêque, Patrick Raulic, Didier Riethmuller, Martine Baudin, Patrice Mathevet, Jean-Luc Brun, Valérie Calenda, Suzy Scholl, Bernard Huynh, Jean-Jacques Baldauf, Philippe Birembaut, Véronique Dalstein, Jean-Paul Bory, CHU Bordeaux [Bordeaux], Plasticité de l'épithélium respiratoire dans les conditions normales et pathologiques - UMR-S 903 ( PERPMP ), Université de Reims Champagne-Ardenne ( URCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne ( URCA ) -Université de Picardie Jules Verne ( UPJV ) -Université de Reims Champagne-Ardenne ( URCA ) -Université de Picardie Jules Verne ( UPJV ) -CHU de Reims - Hôpital Maison Blanche, Service de Gynécologie-Obstétrique, CHU Pontchaillou [Rennes], Service de gynécologie–obstétrique, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Service de Génétique Oncologique, INSTITUT CURIE, Service de gynécologie obstétrique, Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Plasticité de l'épithélium respiratoire dans les conditions normales et pathologiques - UMR-S 903 (PERPMP), Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims)-Institut National de la Santé et de la Recherche Médicale (INSERM)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA), Service de Gynécologie et Obstétrique [Rennes] = Gynaecology [Rennes], Institut Curie [Paris], Service de Gynécologie Obstétrique, Médecine Foetale et Stérilité Conjugale - Chirurgie Gynécologie et Oncologique [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Université de Reims Champagne-Ardenne ( URCA ) -Centre Hospitalier Universitaire de Reims ( CHU Reims ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne ( URCA ) -Université de Picardie Jules Verne ( UPJV ) -Université de Reims Champagne-Ardenne ( URCA ) -Université de Picardie Jules Verne ( UPJV ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) ( CEF2P / CARCINO ), and Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté [COMUE] ( UBFC ) -Université de Franche-Comté ( UFC )

Subjects
MESH: Immunotherapy, Uterine Cervical Neoplasms, MESH : Cervical Intraepithelial Neoplasia, Gastroenterology, MESH: Cancer Vaccines, Targeted immunotherapy, 0302 clinical medicine, Cytology, MESH : Female, human papillomavirus, [ SDV.MHEP.GEO ] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, MESH: Treatment Outcome, Colposcopy, 0303 health sciences, medicine.diagnostic_test, MESH : Cancer Vaccines, Obstetrics and Gynecology, virus diseases, female genital diseases and pregnancy complications, 3. Good health, MESH: Uterine Cervical Neoplasms, Treatment Outcome, MESH : Immunotherapy, 030220 oncology & carcinogenesis, MESH : Vaginal Smears, Female, Immunotherapy, medicine.symptom, medicine.medical_specialty, MESH: Vaginal Smears, MESH : Uterine Cervical Neoplasms, MESH : Treatment Outcome, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, cervical intraepithelial neoplasia, Cervical intraepithelial neoplasia, Cancer Vaccines, Lesion, 03 medical and health sciences, Internal medicine, medicine, Humans, Human papillomavirus, 030304 developmental biology, Vaginal Smears, Gynecology, MESH: Humans, business.industry, MESH : Humans, Uterine Cervical Dysplasia, medicine.disease, Clinical trial, High Grade Cervical Intraepithelial Neoplasia, targeted immunotherapy, business, MESH: Cervical Intraepithelial Neoplasia, MESH: Female
Abstract

International audience; OBJECTIVE: We sought to evaluate the safety and efficacy of TG4001 in patients with human papillomavirus (HPV) 16-related cervical intraepithelial neoplasia (CIN) 2/3 at 6 and 12 months. STUDY DESIGN: In all, 21 patients with HPV 16-related CIN 2/3 received 3 weekly subcutaneous injections of TG4001. Regression of the CIN 2/3 lesion and the clearance of HPV 16 infection were monitored by cytology, colposcopy, and HPV DNA/messenger RNA (mRNA) detection. A clinical response was defined by no CIN 2/3 found on conization, or no conization performed because not suspected at cytology or colposcopy. RESULTS: Ten patients (48%) were evaluated as clinical responders at month 6. Nine patients experienced an improvement of their HPV 16 infection, by mRNA ± DNA eradication. HPV 16 mRNA clearance was associated with CIN 2/3 cytologic and colposcopic regression in 7 of 10 patients. At month 12, 7 of 8 patients without conization reported neither suspicion of CIN 2/3 relapse nor HPV 16 infection. The remaining patient was lost to follow-up. CONCLUSION: These promising data warrant further development of TG4001 in CIN 2/3 treatment.

Published
2011
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3. A combination of transposable elements and magnetic cell sorting provides a very efficient transgenesis system for chicken primary erythroid progenitors

Author

Koichi Kawakami, Camila Mejia-Pous, Olivier Gandrillon, Joanna Koszela, José Viñuelas, Claudine Faure, Yoshiko Takahashi, Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Biologie Fonctionnelle, Insectes et Interactions (BF2I), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA), Department of Geophysics [Sendai], Tohoku University [Sendai], LNCC, the CNRS, the UCBL, the Region Rhône Alpes, the IXXI and the ARC, Centre de génétique et de physiologie moléculaire et cellulaire ( CGPhiMC ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Biologie Fonctionnelle, Insectes et Interactions ( BF2I ), Institut National de la Recherche Agronomique ( INRA ) -Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), and Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Université de Lyon-Institut National des Sciences Appliquées ( INSA )

Subjects
MESH : DNA, Complementary, MESH: Immunotherapy, Cell Separation, MESH: Base Sequence, Polymerase Chain Reaction, Retrovirus, MESH: Genetic Vectors, Complementary, MESH: Animals, Transgenes, MESH : Polymerase Chain Reaction, Erythroid Precursor Cells, Cells, Cultured, Genetics, MESH : Immunoglobulin Fc Fragments, biology, Methodology Article, Cell sorting, MESH : Genetic Vectors, Cell biology, Transgenesis, MESH : Immunotherapy, MESH: Immunization, Immunotherapy, SDV:BBM:BM, Stem cell, Biotechnology, Plasmids, Transposable element, Animals, Base Sequence, Cloning, Molecular, DNA, Genetic Vectors, Immunization, Immunoglobulin Fc Fragments, Recombinant Fusion Proteins, Solubility, Cell type, MESH : Cloning, Molecular, MESH : Recombinant Fusion Proteins, lcsh:Biotechnology, Transgene, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Transfection, MESH: Immunoglobulin Fc Fragments, lcsh:TP248.13-248.65, MESH: Recombinant Fusion Proteins, MESH: Cloning, Molecular, MESH : Solubility, MESH: Polymerase Chain Reaction, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH : Immunization, MESH: DNA, Complementary, biology.organism_classification, MESH: Solubility, Mutagenesis, Insertional, DNA Transposable Elements, MESH : Base Sequence, MESH : Animals, Chickens
Abstract

Background Stable transgenesis is an undeniable key to understanding any genetic system. Retrovirus-based insertional strategies, which feature several technical challenges when they are used, are often limited to one particular species, and even sometimes to a particular cell type as the infection depends on certain cellular receptors. A universal-like system, which would allow both stable transgene expression independent of the cell type and an efficient sorting of transfected cells, is required when handling cellular models that are incompatible with retroviral strategies. Results We report here on the combination of a stable insertional transgenesis technique, based on the Tol2 transposon system together with the magnetic cell sorting (MACS) technique, which allows specific selection of cells carrying the transgene in an efficient, reliable and rapid way. Conclusion This new Tol2/MACS system leads to stable expression in a culture of primary chicken erythroid cells highly enriched in cells expressing the transgene of interest. This system could be used in a wide variety of vertebrate species.

Published
2009
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4. 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
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