与重组的过敏原-药物偶联物相比,重组的Der 1特异性过敏原毒素对过敏原反应性IgG+杂交瘤的杀伤能力更强。

IF 4.1 Q2 IMMUNOLOGY
A K Daramola, O A Akinrinmade, E A Fajemisin, K Naran, N Mthembu, S Hadebe, F Brombacher, A M Huysamen, O E Fadeyi, R Hunter, S Barth
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引用次数: 0

摘要

目前的治疗哮喘有助于缓解临床症状,但不能治愈疾病。在这项研究中,我们探索了一种新的治疗方法来治疗尘螨过敏原Der p1诱导的哮喘,旨在消除参与Der p1记忆IgE反应的特定b细胞群。材料和方法:为了实现这一目标,我们开发并评估了两种不同的基于proDer p1的融合蛋白;一种过敏原毒素(proDer p1 - eta)和一种过敏原药物偶联物(ADC) (proDer p1 - snap - aurif)抗Der p1反应性杂杂瘤作为Der p1反应性人b细胞的体外模型。该策略包括使用proDer p1过敏原作为细胞特异性配体,选择性地将细菌蛋白毒素假单胞菌外毒素a (ETA)或合成小分子毒素Auristatin F (AURIF)递送到Der p1反应细胞的细胞质中,以实现高效的细胞杀伤。结果:因此,我们证明重组proDer p1融合蛋白可以选择性地与hdm致敏小鼠的Der p1反应性杂交瘤和原代IgG1+ b细胞结合。proDer p1 - eta '和proDer p1 - snap - aurif对Der p1反应性杂杂瘤细胞的选择性细胞毒活性证实了它们的治疗潜力。与ADC相比,过敏原毒素显示出优越的细胞毒活性,IC50值为个位数纳摩尔值。讨论:总之,本研究的概念验证实验为屋尘螨驱动的过敏性哮喘患者的治疗提供了一种有希望的方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

A recombinant Der p 1-specific allergen-toxin demonstrates superior killing of allergen-reactive IgG<sup>+</sup> hybridomas in comparison to its recombinant allergen-drug conjugate.

A recombinant Der p 1-specific allergen-toxin demonstrates superior killing of allergen-reactive IgG<sup>+</sup> hybridomas in comparison to its recombinant allergen-drug conjugate.

A recombinant Der p 1-specific allergen-toxin demonstrates superior killing of allergen-reactive IgG<sup>+</sup> hybridomas in comparison to its recombinant allergen-drug conjugate.

A recombinant Der p 1-specific allergen-toxin demonstrates superior killing of allergen-reactive IgG+ hybridomas in comparison to its recombinant allergen-drug conjugate.

Introduction: 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.

Materials and methods: 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 (ADC) (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.

Results: 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 ADC.

Discussions: 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.

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