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Transcutaneous penetration of a single-chain variable fragment (scFv) compared to a full-size antibody: potential tool for atopic dermatitis (AD) treatment
Allergy, Asthma & Clinical Immunology ( IF 2.6 ) Pub Date : 2021-07-19 , DOI: 10.1186/s13223-021-00574-x
Audrey Baylet 1, 2 , Raoul Vyumvuhore 2 , Marine Laclaverie 2 , Laëtitia Marchand 2 , Carine Mainzer 2 , Sylvie Bordes 2 , Brigitte Closs-Gonthier 2 , Laurent Delpy 1
Affiliation  

Currently, several biologics are used for the treatment of cutaneous pathologies such as atopic dermatitis (AD), psoriasis or skin cancers. The main administration routes are subcutaneous and intravenous injections. However, little is known about antibody penetration through the skin. The aim was to study the transcutaneous penetration of a reduced-size antibody as a single-chain variable fragment (scFv) compared to a whole antibody (Ab) and to determine its capacity to neutralize an inflammatory cytokine involved in AD such as human interleukin-4 (hIL-4). Transcutaneous penetration was evaluated by ex vivo studies on tape-stripped pig ear skin. ScFv and Ab visualization through the skin was measured by Raman microspectroscopy. In addition, hIL-4 neutralization was studied in vitro using HEK-Blue™ IL-4/IL-13 cells and normal human keratinocytes (NHKs). After 24 h of application, analysis by Raman microspectroscopy showed that scFv penetrated into the upper dermis while Ab remained on the stratum corneum. In addition, the anti-hIL4 scFv showed very efficient and dose-dependent hIL-4 neutralization. Thus, scFv penetrates through to the upper papillary dermis while Ab mostly remains on the surface, the anti-hIL4 scFv also neutralizes its target effectively suggesting its potential use as topical therapy for AD.

中文翻译:

与全尺寸抗体相比,单链可变片段 (scFv) 的经皮渗透:特应性皮炎 (AD) 治疗的潜在工具

目前,有几种生物制剂用于治疗皮肤病,例如特应性皮炎 (AD)、牛皮癣或皮肤癌。主要给药途径为皮下注射和静脉注射。然而,关于抗体穿透皮肤的知识知之甚少。目的是研究与完整抗体 (Ab) 相比,作为单链可变片段 (scFv) 的减小尺寸抗体的经皮渗透,并确定其中和 AD 中涉及的炎性细胞因子(如人白细胞介素)的能力。 4 (hIL-4)。通过对胶带剥离的猪耳朵皮肤的离体研究来评估经皮渗透。通过拉曼显微光谱法测量通过皮肤的 ScFv 和 Ab 可视化。此外,使用 HEK-Blue™ IL-4/IL-13 细胞和正常人角质形成细胞 (NHK) 在体外研究了 hIL-4 中和。应用 24 小时后,拉曼显微光谱分析表明,scFv 渗透到真皮上部,而 Ab 保留在角质层上。此外,抗 hIL4 scFv 显示出非常有效和剂量依赖性的 hIL-4 中和作用。因此,scFv 渗透到上乳头状真皮,而 Ab 主要保留在表面,抗 hIL4 scFv 也有效地中和了其靶标,表明其作为 AD 局部治疗的潜在用途。
更新日期:2021-07-19
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