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
K1 Allergy
K1 Der p 1
K1 Immunotoxins
K1 Basophils
K1 Cell death
K1 Pyroglyphidae
K1 Hipersensibilidad
K1 Inmunotoxinas
K1 Basófilos
K1 Muerte celular
AB 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.
PB Springer Nature
YR 2020
FD 2020-07-23
LK http://hdl.handle.net/10668/4059
UL http://hdl.handle.net/10668/4059
LA en
NO Lázaro-Gorines R, López-Rodríguez JC, Benedé S, González M, Mayorga C, Vogel L, et al. Der p 1-based immunotoxin as potential tool for the treatment of dust mite respiratory allergy. Sci Rep. 2020 Jul 23;10(1):12255
DS RISalud
RD Apr 9, 2025