%0 Journal Article
%A Lázaro-Gorines, Rodrigo
%A López-Rodríguez, Juan Carlos
%A Benedé, Sara
%A González, Miguel
%A Mayorga, Cristobalina
%A Vogel, Lothar
%A Martínez-Del-Pozo, Álvaro
%A Lacadena, Javier
%A Villalba, Mayte
%T Der p 1-based immunotoxin as potential tool for the treatment of dust mite respiratory allergy
%D 2020
%U http://hdl.handle.net/10668/4059
%X Immunotoxins appear as promising therapeutic molecules, alternative to allergen-specific-immunotherapy. In this work, we achieved the development of a protein chimera able to promote specific cell death on effector 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 purified from the yeast Pichia pastoris. Der p 1-protease activity and α-sarcin ribonucleolytic action were effectively conserved in proDerp1αS. Immunotoxin impact was assayed by using effector 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 purified basophils from sensitized patients. However, proDerp1αS did not cause any cytotoxic effect on these cells, apparently due to its lack of internalization after their surface IgE-binding, 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 specific, second-generation of immunotoxins following proDerp1αS, is further discussed.
%K Allergy
%K Der p 1
%K Immunotoxins
%K Basophils
%K Cell death
%K Pyroglyphidae
%K Hipersensibilidad
%K Inmunotoxinas
%K Basófilos
%K Muerte celular
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