A recombinant Der p 1-specific allergen-toxin demonstrates superior killing of allergen-reactive IgG+ hybridomas in comparison to its recombinant allergen-drug conjugate. Daramola, A K, Akinrinmade, O A, Fajemisin, E A, Naran, K, Mthembu, N, Hadebe, S, Brombacher, F, Huysamen, A M, Fadeyi, O E, Hunter, R, & Barth, S Immunotherapy advances, 3(1):ltac023, Immunother Adv, jan, 2022. ![A recombinant Der p 1-specific allergen-toxin demonstrates superior killing of allergen-reactive IgG+ hybridomas in comparison to its recombinant allergen-drug conjugate [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex Current treatments for asthma help to alleviate clinical symptoms but do not cure the disease. In this study, we explored a novel therapeutic approach for the treatment of house dust mite allergen Der p 1induced asthma by aiming to eliminate specific population of B-cells involved in memory IgE response to Der p 1. To achieve this aim, we developed and evaluated two different proDer p 1-based fusion proteins; an allergen-toxin (proDer p 1-ETA) and an allergen drug conjugate (proDer p 1-SNAP-AURIF) against Der p 1 reactive hybridomas as an in vitro model for Der p 1 reactive human B-cells. The strategy involved the use of proDer p 1 allergen as a cell-specific ligand to selectively deliver the bacterial protein toxin Pseudomonas exotoxin A (ETA) or the synthetic small molecule toxin Auristatin F (AURIF) into the cytosol of Der p 1-reactive cells for highly efficient cell killing. As such, we demonstrated recombinant proDer p 1-fusion proteins were selectively bound by Der p 1-reactive hybridomas as well as primary IgG1 + B cells from HDM sensitized mice. The therapeutic potential of proDer p 1-ETA` and proDer p 1-SNAP-AURIF was confirmed by their selective cytotoxic activities on Der p 1 reactive hybridoma cells. The allergen-toxin demonstrated superior cytotoxic activity, with IC50 values in the single digit nanomolar value, compared to the allergen drug conjugate. Altogether, the proof-of-concept experiments in this study provide a promising approach for the treatment of patients with house dust mite-driven allergic asthma.
@article{Daramola2022,
abstract = {Current treatments for asthma help to alleviate clinical symptoms but do not cure the disease. In this study, we explored a novel therapeutic approach for the treatment of house dust mite allergen Der p 1induced asthma by aiming to eliminate specific population of B-cells involved in memory IgE response to Der p 1. To achieve this aim, we developed and evaluated two different proDer p 1-based fusion proteins; an allergen-toxin (proDer p 1-ETA) and an allergen drug conjugate (proDer p 1-SNAP-AURIF) against Der p 1 reactive hybridomas as an in vitro model for Der p 1 reactive human B-cells. The strategy involved the use of proDer p 1 allergen as a cell-specific ligand to selectively deliver the bacterial protein toxin Pseudomonas exotoxin A (ETA) or the synthetic small molecule toxin Auristatin F (AURIF) into the cytosol of Der p 1-reactive cells for highly efficient cell killing. As such, we demonstrated recombinant proDer p 1-fusion proteins were selectively bound by Der p 1-reactive hybridomas as well as primary IgG1 + B cells from HDM sensitized mice. The therapeutic potential of proDer p 1-ETA` and proDer p 1-SNAP-AURIF was confirmed by their selective cytotoxic activities on Der p 1 reactive hybridoma cells. The allergen-toxin demonstrated superior cytotoxic activity, with IC50 values in the single digit nanomolar value, compared to the allergen drug conjugate. Altogether, the proof-of-concept experiments in this study provide a promising approach for the treatment of patients with house dust mite-driven allergic asthma.},
author = {Daramola, A K and Akinrinmade, O A and Fajemisin, E A and Naran, K and Mthembu, N and Hadebe, S and Brombacher, F and Huysamen, A M and Fadeyi, O E and Hunter, R and Barth, S},
doi = {10.1093/IMMADV/LTAC023},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Daramola et al. - 2022 - A recombinant Der p 1-specific allergen-toxin demonstrates superior killing of allergen-reactive IgG hybridomas.pdf:pdf},
issn = {2732-4303},
journal = {Immunotherapy advances},
keywords = {A K Daramola,MEDLINE,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,O A Akinrinmade,OA,OA{\_}PMC,PMC9912260,PubMed Abstract,S Barth,doi:10.1093/immadv/ltac023,fund{\_}not{\_}ack,original,pmid:36789295},
mendeley-tags = {OA,OA{\_}PMC,fund{\_}not{\_}ack,original},
month = {jan},
number = {1},
pages = {ltac023},
pmid = {36789295},
publisher = {Immunother Adv},
title = {{A recombinant Der p 1-specific allergen-toxin demonstrates superior killing of allergen-reactive IgG+ hybridomas in comparison to its recombinant allergen-drug conjugate}},
url = {https://pubmed.ncbi.nlm.nih.gov/36789295/},
volume = {3},
year = {2022}
}
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To achieve this aim, we developed and evaluated two different proDer p 1-based fusion proteins; an allergen-toxin (proDer p 1-ETA) and an allergen drug conjugate (proDer p 1-SNAP-AURIF) against Der p 1 reactive hybridomas as an in vitro model for Der p 1 reactive human B-cells. The strategy involved the use of proDer p 1 allergen as a cell-specific ligand to selectively deliver the bacterial protein toxin Pseudomonas exotoxin A (ETA) or the synthetic small molecule toxin Auristatin F (AURIF) into the cytosol of Der p 1-reactive cells for highly efficient cell killing. As such, we demonstrated recombinant proDer p 1-fusion proteins were selectively bound by Der p 1-reactive hybridomas as well as primary IgG1 + B cells from HDM sensitized mice. The therapeutic potential of proDer p 1-ETA` and proDer p 1-SNAP-AURIF was confirmed by their selective cytotoxic activities on Der p 1 reactive hybridoma cells. The allergen-toxin demonstrated superior cytotoxic activity, with IC50 values in the single digit nanomolar value, compared to the allergen drug conjugate. 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