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 Pérez, Sara
dc.contributor.authorGonzález, Miguel
dc.contributor.authorMayorga, Cristobalina
dc.contributor.authorVogel, Lothar
dc.contributor.authorMartínez Del Pozo, Álvaro
dc.contributor.authorLacadena García-Gallo, Francisco Javier
dc.contributor.authorVillalba Díaz, María Teresa
dc.date.accessioned2024-01-17T09:52:49Z
dc.date.available2024-01-17T09:52:49Z
dc.date.issued2020-12-01
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 Economia y ́Competitividad
dc.description.sponsorshipInstituto de Salud Carlos III (ISCIII)
dc.description.statuspub
dc.identifier.doi10.1038/s41598-020-69166-w
dc.identifier.doi2045-2322
dc.identifier.officialurlhttps://www.nature.com/articles/s41598-020-69166-w
dc.identifier.urihttps://hdl.handle.net/20.500.14352/93544
dc.issue.number1
dc.journal.titleScientific Reports
dc.language.isoeng
dc.page.initial12255
dc.publisherNature Research
dc.relation.projectID(PR75/18-21563; PR87/19- 22627)
dc.relation.projectIDSAF2017-86483-R
dc.relation.projectIDARADyAL (RD16/0006/0014; RD16/0006/0001)
dc.rights.accessRightsopen access
dc.subject.cdu577.1
dc.subject.keywordAllergens
dc.subject.keywordAnimals
dc.subject.keywordAntigens
dc.subject.keywordDermatophagoides
dc.subject.keywordArthropod Proteins
dc.subject.keywordBasophils
dc.subject.keywordCell Degranulation
dc.subject.keywordCell Line
dc.subject.keywordCells
dc.subject.keywordCultured
dc.subject.keywordCysteine Endopeptidases
dc.subject.keywordDermatophagoides pteronyssinus
dc.subject.keywordDesensitization
dc.subject.keywordImmunologic
dc.subject.keywordHumans
dc.subject.keywordHypersensitivity
dc.subject.keywordImmunoglobulin E
dc.subject.keywordImmunotoxins
dc.subject.keywordRecombinant Proteins
dc.subject.ucmBioquímica (Química)
dc.subject.ucmCiencias Biomédicas
dc.subject.unesco23 Química
dc.titleDer p 1‑based immunotoxin as potential tool for the treatment of dust mite respiratory allergy
dc.typejournal article
dc.type.hasVersionAM
dc.volume.number10
dspace.entity.typePublication
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