Lázaro-Gorines, RodrigoLópez-Rodríguez, Juan CarlosBenedé, SaraGonzález, MiguelMayorga, CristobalinaVogel, LotharMartínez-Del-Pozo, ÁlvaroLacadena, JavierVillalba, Mayte2022-09-192022-09-192020-07-23Lázaro-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):12255http://hdl.handle.net/10668/4059Immunotoxins 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/AllergyDer p 1ImmunotoxinsBasophilsCell deathPyroglyphidaeHipersensibilidadInmunotoxinasBasófilosMuerte celularMedical Subject Headings::Chemicals and Drugs::Biological Factors::Antigens::AllergensMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Chemicals and Drugs::Biological Factors::Antigens::Antigens, DermatophagoidesMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Arthropod ProteinsMedical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Granulocytes::BasophilsMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Exocytosis::Cell DegranulationMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell LineMedical Subject Headings::Anatomy::Cells::Cells, CulturedMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Peptide Hydrolases::Cysteine Proteases::Cysteine EndopeptidasesMedical Subject Headings::Organisms::Eukaryota::Animals::Invertebrates::Arthropods::Arachnida::Acari::Mites::Pyroglyphidae::Dermatophagoides pteronyssinusMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy::Immunosuppression::Desensitization, ImmunologicMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Diseases::Immune System Diseases::HypersensitivityMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Immunoglobulin Isotypes::Immunoglobulin EMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Immunoconjugates::ImmunotoxinsMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Recombinant ProteinsMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Exocytosis::Cell DegranulationMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Deathresearch article32703972open access10.1038/s41598-020-69166-w2045-2322PMC7378242