Transcutaneous penetration of a single-chain variable fragment (scFv) compared to a full-size antibody: potential tool for atopic dermatitis (AD) treatment

Audrey Baylet,Brigitte Closs-Gonthier,Laëtitia Marchand,Sylvie Bordes,Raoul Vyumvuhore,Marine Laclaverie,Carine Mainzer,Laurent Delpy

doi:10.1186/s13223-021-00574-x

Abstract

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.

Highlights

Currently, immunotherapy is used for the treatment of several skin pathologies such as atopic dermatitis (AD), psoriasis (PSO) and cancers, mainly via subcutaneous or intravenous routes
Finding new antibody delivery methods is a challenge and different technologies have emerged in recent years such as microneedle patches, nanoparticles, liposomes or gel formulations
Several modified antibodies are under development to treat cutaneous diseases, but at present, only certolizumab pegol, a PEGylated anti-tumor necrosis factor α antigen-binding fragment (Fab) has been approved (2013) for the treatment of PSO [1]

Summary

Introduction

Immunotherapy is used for the treatment of several skin pathologies such as atopic dermatitis (AD), psoriasis (PSO) and cancers, mainly via subcutaneous or intravenous routes. AD is an inflammatory skin disease with a high and constantly increasing prevalence worldwide (1–3% of adults and 15–20% of children) [2]. This pathology is characterized by a skin barrier default and a Th2 phenotype with secretion of several proinflammatory cytokines such as interleukin-4 (IL-4), IL-5 and IL-13. Different cell populations express the high affinity IgE receptor (FcεRI) and immune complex

Methods

Results

Conclusion