Academic Journal
Engineered exosomes emerging from muscle cells break immune tolerance to HER2 in transgenic mice and induce antigen-specific CTLs upon challenge by human dendritic cells
| العنوان: | Engineered exosomes emerging from muscle cells break immune tolerance to HER2 in transgenic mice and induce antigen-specific CTLs upon challenge by human dendritic cells |
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| المؤلفون: | Anticoli, Simona, Aricò, Eleonora, Arenaccio, Claudia, Manfredi, Francesco, Chiozzini, Chiara, Olivetta, Eleonora, Ferrantelli, Flavia, Lattanzi, Laura, D'Urso, Maria Teresa, Proietti, Enrico, Federico, Maurizio |
| المساهمون: | Anticoli, Simona, Aricò, Eleonora, Arenaccio, Claudia, Manfredi, Francesco, Chiozzini, Chiara, Olivetta, Eleonora, Ferrantelli, Flavia, Lattanzi, Laura, D'Urso, Maria Teresa, Proietti, Enrico, Federico, Maurizio |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | CTL vaccine, Exosome, HER2/neu, Immunological tolerance, Nef, Animal, Cells, Cultured, Dendritic Cell, Human, Immune Tolerance, Immunotherapy, Mice, Transgenic, Muscle, Neoplasm, Receptor, ErbB-2, T-Lymphocytes, Cytotoxic |
| الوصف: | We recently described a novel biotechnological platform for the production of unrestricted cytotoxic T lymphocyte (CTL) vaccines. It relies on in vivo engineering of exosomes, i.e., nanovesicles constitutively released by all cells, with full-length antigens of choice upon fusion with an exosome-anchoring protein referred to as Nefmut. They are produced upon intramuscular injection of a DNA vector and, when uploaded with a viral tumor antigen, were found to elicit an immune response inhibiting the tumor growth in a model of transplantable tumors. However, for a possible application in cancer immunotherapy, a number of key issues remained unmet. Among these, we investigated: (i) whether the immunogenic stimulus induced by the engineered exosomes can break immune tolerance, and (ii) their effectiveness when applied in human system. As a model of immune tolerance, we considered mice transgenic for the expression of activated rat HER2/neu which spontaneously develop adenocarcinomas in all mammary glands. When these mice were injected with a DNA vector expressing the product of fusion between Nefmut and the extracellular domain of HER2/neu, antigen-specific CD8+ T lymphocytes became readily detectable. This immune response associated with a HER2-directed CTL activity and a significant delay in tumor development. On the other hand, through cross-priming experiments, we demonstrated the effectiveness of the engineered exosomes emerging from transfected human primary muscle cells in inducing antigen-specific CTLs. We propose our CTL vaccine platform as part of new immunotherapy strategies against tumors expressing self-antigens, i.e., products highly expressed in oncologic lesions but tolerated by the immune system. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/wos/WOS:000423123100009; volume:96; issue:2; firstpage:211-221; journal:JOURNAL OF MOLECULAR MEDICINE; http://hdl.handle.net/11590/374106; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85039862371 |
| DOI: | 10.1007/s00109-017-1617-2 |
| الاتاحة: | http://hdl.handle.net/11590/374106 https://doi.org/10.1007/s00109-017-1617-2 |
| رقم الانضمام: | edsbas.B3FB0076 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1007/s00109-017-1617-2 |
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