2026-06-14T03:44:57Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/180812024-11-28T14:50:12Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927

00925njm 22002777a 4500 dc Lázaro-Gorines, Rodrigo author López-Rodríguez, Juan Carlos author Benedé, Sara author González, Miguel author Mayorga, Cristobalina author Vogel, Lothar author Martínez-Del-Pozo, Álvaro author Lacadena, Javier author Villalba, Mayte author 2020-07-23 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. 10.1038/s41598-020-69166-w 2045-2322 Scientific Reports http://hdl.handle.net/10668/4059 32703972 http://hdl.handle.net/20.500.12105/18081 Allergy Der p 1 Immunotoxins Basophils Cell death Pyroglyphidae Hipersensibilidad Inmunotoxinas Basófilos Muerte celular Der p 1-based immunotoxin as potential tool for the treatment of dust mite respiratory allergy