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Título:
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Der p 1 based immunotoxin as potential tool for the treatment of dust mite respiratory allergy
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Autores:
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Lázaro Gorines, Rodrigo ;
López Rodríguez, Juan Carlos ;
Benedé, Sara ;
González, Miguel ;
Mayorga, Cristobalina ;
Vogel, Lothar ;
Martínez del Pozo, Álvaro ;
Lacadena, Javier ;
Villalba, Mayte
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Tipo de documento:
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texto impreso
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Editorial:
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Nature Research, 2020-07-23
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Dimensiones:
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application/pdf
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Nota general:
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info:eu-repo/semantics/openAccess
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Idiomas:
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Palabras clave:
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Estado = Publicado
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Materia = Ciencias: Química: Biología molecular
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Materia = Ciencias: Química: Bioquímica
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Tipo = Artículo
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Resumen:
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Immunotoxins appear as promising therapeutic molecules, alternative to allergen-specifcimmunotherapy. In this work, we achieved the development of a protein chimera able to promote specifc cell death on efector cells involved in the allergic reaction. Der p 1 allergen was chosen as cell-targeting domain and the powerful ribotoxin ?-sarcin as the toxic moiety. The resultant construction, named proDerp1?S, was produced and purifed from the yeast Pichia pastoris. Der p 1-protease activity and ?-sarcin ribonucleolytic action were efectively conserved in proDerp1?S. Immunotoxin impact was assayed by using efector cells sensitized with house dust mite-allergic sera. Cell degranulation and death, triggered by proDerp1?S, was exclusively observed on Der p 1 sera sensitized-humRBL-2H3 cells, but not when treated with non-allergic sera. Most notably, equivalent IgE-binding and degranulation were observed with both proDerp1?S construct and native Der p 1 when using purifed basophils from sensitized patients. However, proDerp1?S did not cause any cytotoxic efect on these cells, apparently due to its lack of internalization after their surface IgEbinding, showing the complex in vivo panorama governing allergic reactions. In conclusion, herein we present proDerp1?S as a proof of concept for a potential and alternative new designs of therapeutic tools for allergies. Development of new, and more specifc, second-generation of immunotoxins following proDerp1?S, is further discussed.
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En línea:
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https://eprints.ucm.es/id/eprint/62185/1/LazaroGorines2020_ScientificReports.pdf
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