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Enhancing Antitumor Immune Responses by Optimized Combinations of Cell-penetrating Peptide-based Vaccines and Adjuvants.
Belnoue, Elodie; Di Berardino-Besson, Wilma; Gaertner, Hubert; Carboni, Susanna; Dunand-Sauthier, Isabelle; Cerini, Fabrice; Suso-Inderberg, Else-Marit; Wälchli, Sébastien; König, Stéphane; Salazar, Andres M; Hartley, Oliver; Dietrich, Pierre-Yves; Walker, Paul R; Derouazi, Madiha.
Afiliación
  • Belnoue E; Amal Therapeutics, Geneva, Switzerland.
  • Di Berardino-Besson W; Center of Oncology, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
  • Gaertner H; Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
  • Carboni S; Amal Therapeutics, Geneva, Switzerland.
  • Dunand-Sauthier I; Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
  • Cerini F; Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
  • Suso-Inderberg EM; Department of Cellular Therapy, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
  • Wälchli S; Department of Cellular Therapy, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
  • König S; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
  • Salazar AM; Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland.
  • Hartley O; Oncovir, Washington DC, USA.
  • Dietrich PY; Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
  • Walker PR; Center of Oncology, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
  • Derouazi M; Center of Oncology, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
Mol Ther ; 24(9): 1675-85, 2016 09.
Article en En | MEDLINE | ID: mdl-27377043
Cell penetrating peptides (CPPs) from the protein ZEBRA are promising candidates to exploit in therapeutic cancer vaccines, since they can transport antigenic cargos into dendritic cells and induce tumor-specific T cells. Employing CPPs for a given cancer indication will require engineering to include relevant tumor-associated epitopes, administration with an appropriate adjuvant, and testing for antitumor immunity. We assessed the importance of structural characteristics, efficiency of in vitro transduction of target cells, and choice of adjuvant in inducing the two key elements in antitumor immunity, CD4 and CD8 T cells, as well as control of tumor growth in vivo. Structural characteristics associated with CPP function varied according to CPP truncations and cargo epitope composition, and correlated with in vitro transduction efficiency. However, subsequent in vivo capacity to induce CD4 and CD8 T cells was not always predicted by in vitro results. We determined that the critical parameter for in vivo efficacy using aggressive mouse tumor models was the choice of adjuvant. Optimal pairing of a particular ZEBRA-CPP sequence and antigenic cargo together with adjuvant induced potent antitumor immunity. Our results highlight the irreplaceable role of in vivo testing of novel vaccine constructs together with adjuvants to select combinations for further development.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adyuvantes Inmunológicos / Vacunas contra el Cáncer / Péptidos de Penetración Celular / Neoplasias Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Mol Ther Asunto de la revista: BIOLOGIA MOLECULAR / TERAPEUTICA Año: 2016 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adyuvantes Inmunológicos / Vacunas contra el Cáncer / Péptidos de Penetración Celular / Neoplasias Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Mol Ther Asunto de la revista: BIOLOGIA MOLECULAR / TERAPEUTICA Año: 2016 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Estados Unidos