RT Journal Article
T1 Der p 1 based immunotoxin as potential tool for the treatment of dust mite respiratory allergy
A1 Lázaro Gorines, Rodrigo
A1 López Rodríguez, Juan Carlos
A1 Benedé, Sara
A1 González, Miguel
A1 Mayorga, Cristobalina
A1 Vogel, Lothar
A1 Martínez del Pozo, Álvaro
A1 Lacadena, Javier
A1 Villalba, Mayte
AB 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 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.
PB Nature Research
SN 2045-2322
YR 2020
FD 2020-07-23
LK https://hdl.handle.net/20.500.14352/6551
UL https://hdl.handle.net/20.500.14352/6551
LA eng
NO Universidad Complutense de Madrid
NO Ministerio de Economía y Competitividad
NO Instituto de Salud Carlos III (ISCIII)
DS Docta Complutense
RD 6 may 2024