Cancer vaccines: designing artificial synthetic long peptides to improve presentation of class I and class II T cell epitopes by dendritic cells
| Autor: | Léa Paolini, Olivier Adotevi, Maud Charpentier, E Dupel, Agnès Fortun, Emilie Dupré, Catherine Rabu, Nathalie Labarrière, Céline Beauvillain, L. Rangan, Jean-Baptiste Latouche, François Lang, Laetitia Florenceau |
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| Přispěvatelé: | Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), LabEX IGO Immunothérapie Grand Ouest, 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), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes (UN)-Université d'Angers (UA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Anti-Tumor Immunosurveillance and Immunotherapy (CRCINA-ÉQUIPE 3), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), LabEx IGO 'Immunotherapy, Graft, Oncology' [Nantes], Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Département de génétique [CHU Rouen] (Centre Normandie de Génomique et de Médecine Personnalisée), CHU Rouen, Normandie Université (NU)-Normandie Université (NU), This work was carried out with the support of the LabEx IGO project (n° ANR-11-LABX-0016–01) funded by the «Investissements d’Avenir» French Government program, managed by the French National Research Agency (ANR)., ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011), Bernardo, Elizabeth, Laboratoires d'excellence - Immunothérapies Grand Ouest - - IGO2011 - ANR-11-LABX-0016 - LABX - VALID, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Nantes Université (Nantes Univ) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
lcsh:Immunologic diseases. Allergy [SDV.IMM] Life Sciences [q-bio]/Immunology T cell Immunology Peptide [SDV.CAN]Life Sciences [q-bio]/Cancer Human leukocyte antigen Biology Cancer vaccines lcsh:RC254-282 Epitope 03 medical and health sciences 0302 clinical medicine [SDV.CAN] Life Sciences [q-bio]/Cancer Antigen medicine melanoma Immunology and Allergy Cytotoxic T cell ComputingMilieux_MISCELLANEOUS Original Research chemistry.chemical_classification Cancer [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens synthetic long peptides 3. Good health Vaccination 030104 developmental biology medicine.anatomical_structure Oncology chemistry 030220 oncology & carcinogenesis [SDV.IMM]Life Sciences [q-bio]/Immunology [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy lcsh:RC581-607 |
| Zdroj: | OncoImmunology OncoImmunology, Taylor & Francis, 2019, 8 (4), pp.e1560919. ⟨10.1080/2162402X.2018.1560919⟩ OncoImmunology, Taylor & Francis, 2019, pp.e1560919-2. ⟨10.1080/2162402x.2018.1560919⟩ Oncoimmunology OncoImmunology, Vol 8, Iss 4 (2019) OncoImmunology, 2019, pp.e1560919-2. ⟨10.1080/2162402x.2018.1560919⟩ |
| ISSN: | 2162-4011 2162-402X |
| Popis: | International audience; There is now a consensus that efficient peptide vaccination against cancer requires that peptides should (i) be exclusively presented by professional APC and (ii) stimulate both CD4 and CD8-specific T cell responses. To this aim, in recent trials, patients were vaccinated with pools of synthetic long peptides (SLP) (15-30 aa long) composed of a potential class I epitope(s) elongated at both ends with native antigen sequences to also provide a potential class II epitope(s). Using MELOE-1 as a model antigen, we present an alternative strategy consisting in linking selected class I and class II epitopes with an artificial cathepsin-sensitive linker to improve epitope processing and presentation by DC. We provide evidence that some linker sequences used in our artificial SLPs (aSLPs) could increase up to 100-fold the cross-presentation of class I epitopes to CD8-specific T cell clones when compared to cross-presentation of the corresponding native long peptide. Presentation of class II epitopes were only slightly increased. We confirmed this increased cross-presentation after in vitro stimulation of PBMC from healthy donors with aSLP and assessment of CD8-specific responses and also in vivo following aSLP vaccination of HLA*A0201/HLA-DRB0101 transgenic mice. Finally, we provide some evidence that vaccination with aSLP could inhibit the growth of transplanted tumors in mice. Our data thus support the use of such aSLPs in future cancer vaccination trials to improve anti-tumor CD8 T cell responses and therapeutic efficacy. ARTICLE HISTORY |
| Databáze: | OpenAIRE |
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