Der p 1 based immunotoxin as potential tool for the treatment of dust mite respiratory allergy

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dc.contributor.authorLázaro Gorines, Rodrigo
dc.contributor.authorLópez Rodríguez, Juan Carlos
dc.contributor.authorBenedé, Sara
dc.contributor.authorGonzález, Miguel
dc.contributor.authorMayorga, Cristobalina
dc.contributor.authorVogel, Lothar
dc.contributor.authorMartínez del Pozo, Álvaro
dc.contributor.authorLacadena, Javier
dc.contributor.authorVillalba, Mayte
dc.date.accessioned2023-06-16T15:23:19Z
dc.date.available2023-06-16T15:23:19Z
dc.date.issued2020-07-23
dc.description.abstractImmunotoxins 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 α-sarcin as the toxic moiety. The resultant construction, named proDerp1αS, was produced and purifed from the yeast Pichia pastoris. Der p 1-protease activity and α-sarcin ribonucleolytic action were efectively conserved in proDerp1αS. Immunotoxin impact was assayed by using efector cells sensitized with house dust mite-allergic sera. Cell degranulation and death, triggered by proDerp1αS, 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 proDerp1αS construct and native Der p 1 when using purifed basophils from sensitized patients. However, proDerp1αS 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 proDerp1αS 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 proDerp1αS, is further discussed.
dc.description.departmentDepto. de Bioquímica y Biología Molecular
dc.description.facultyFac. de Ciencias Químicas
dc.description.refereedTRUE
dc.description.sponsorshipUniversidad Complutense de Madrid
dc.description.sponsorshipMinisterio de Economía y Competitividad
dc.description.sponsorshipInstituto de Salud Carlos III (ISCIII)
dc.description.statuspub
dc.eprint.idhttps://eprints.ucm.es/id/eprint/62185
dc.identifier.doi10.1038/s41598-020-69166-w
dc.identifier.issn2045-2322
dc.identifier.officialurlhttps://www.nature.com/articles/s41598-020-69166-w.pdf
dc.identifier.urihttps://hdl.handle.net/20.500.14352/6551
dc.issue.number12255
dc.journal.titleScientific reports
dc.language.isoeng
dc.page.final14
dc.page.initial1
dc.publisherNature Research
dc.relation.projectID(PR75/18-21563; PR87/19- 22627)
dc.relation.projectIDSAF2017-86483-R
dc.relation.projectID(RD16/0006/0014; RD16/0006/0001)
dc.rights.accessRightsopen access
dc.subject.cdu577.1
dc.subject.keywordAntifungal Proteins
dc.subject.keywordAspergillus Fischeri
dc.subject.keywordRicin
dc.subject.ucmBiología molecular (Química)
dc.subject.ucmBioquímica (Química)
dc.titleDer p 1 based immunotoxin as potential tool for the treatment of dust mite respiratory allergy
dc.typejournal article
dc.volume.number10
dspace.entity.typePublication
relation.isAuthorOfPublicationb9515131-fd92-4e57-923d-84da1d3bc75e
relation.isAuthorOfPublication.latestForDiscoveryb9515131-fd92-4e57-923d-84da1d3bc75e
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