Memory and Effector CD8 T-cell Responses After Nanoparticle Vaccination of Melanoma Patients
| Autor: | Christine Geldhof, Uwe Trefzer, Katrin Baumann Conzett, Daniel E. Speiser, Verena Voelter, Alexander Knuth, Peter Walden, Reinhard Dummer, Katrin Schwarz, Jörg Willers, Alfred Zippelius, Pedro Romero, Thomas M. Kündig, Gabriela Senti, Estelle Devevre, Vania Manolova, Petra Baumgaertner, David Guggisberg, Martin F. Bachmann, Wolfram Sterry, Jean Philippe Cerottini |
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| Přispěvatelé: | University of Zurich, Université de Lausanne (UNIL), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University Hospital Basel [Basel], University hospital of Zurich [Zurich], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV) |
| Rok vydání: | 2010 |
| Předmět: |
Male
Cancer Research Skin Neoplasms [SDV]Life Sciences [q-bio] medicine.medical_treatment CD8-Positive T-Lymphocytes Lymphocyte Activation Mice 0302 clinical medicine T-Lymphocyte Subsets Immunology and Allergy Cytotoxic T cell 1306 Cancer Research Melanoma Cells Cultured 0303 health sciences 10177 Dermatology Clinic Cell Differentiation Middle Aged 3. Good health Treatment Outcome 3004 Pharmacology Oligodeoxyribonucleotides 030220 oncology & carcinogenesis 2723 Immunology and Allergy Female Adult Immunology Mice Transgenic 610 Medicine & health Cancer Vaccines 03 medical and health sciences MART-1 Antigen Immune system Antigen HLA-A2 Antigen medicine Animals Humans Vaccines Virus-Like Particle Aged 030304 developmental biology Pharmacology 2403 Immunology Innate immune system business.industry Immunotherapy Peptide Fragments Immunization 10032 Clinic for Oncology and Hematology Nanoparticles business Immunologic Memory [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology CD8 Ex vivo |
| Zdroj: | Journal of Immunotherapy Journal of Immunotherapy, Lippincott, Williams & Wilkins, 2010, 33 (8), pp.848-858. ⟨10.1097/CJI.0b013e3181f1d614⟩ |
| ISSN: | 1524-9557 1537-4513 |
| Popis: | International audience; Induction of cytotoxic CD8 T-cell responses is enhanced by the exclusive presentation of antigen through dendritic cells, and by innate stimuli, such as toll-like receptor ligands. On the basis of these 2 principles, we designed a vaccine against melanoma. Specifically, we linked the melanoma-specific Melan-A/Mart-1 peptide to virus-like nanoparticles loaded with A-type CpG, a ligand for toll-like receptor 9. Melan-A/Mart-1 peptide was cross-presented, as shown in vitro with human dendritic cells and in HLA-A2 transgenic mice. A phase I/II study in stage II-IV melanoma patients showed that the vaccine was well tolerated, and that 14/22 patients generated ex vivo detectable T-cell responses, with in part multifunctional T cells capable to degranulate and produce IFN-γ, TNF-α, and IL-2. No significant influence of the route of immunization (subcutaneous versus intradermal) nor dosing regimen (weekly versus daily clusters) could be observed. It is interesting to note that, relatively large fractions of responding specific T cells exhibited a central memory phenotype, more than what is achieved by other nonlive vaccines. We conclude that vaccination with CpG loaded virus-like nanoparticles is associated with a human CD8 T-cell response with properties of a potential long-term immune protection from the disease. |
| Databáze: | OpenAIRE |
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