Preliminary Investigation and Therapeutic Efficacy Determination of a Novel Anti-IL-17A Antibody, Indikizumab.

IF 5.3 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Biologics : Targets & Therapy Pub Date : 2024-09-17 eCollection Date: 2024-01-01 DOI:10.2147/BTT.S477752

Ashok Kumar Patra, Shreenath Nayak, Anandita Moharana, Purusottam Ojha, Sanjeet Kumar Das, Jabed Akhtar, Bishwaranjan Giri, Sujay Singh

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Abstract

Purpose: The study aimed to develop and characterize Indikizumab, a novel humanized anti-IL-17A monoclonal antibody (mAb), for potential therapeutic use in inflammatory indications such as psoriasis, psoriatic arthritis, rheumatoid arthritis, and ankylosing spondylitis.

Methods: The research involved the purification of IL-17 isoforms, epitope mapping, affinity ranking, and comparative binding assessment of anti-IL-17 antibodies. The study also included cell-based neutralization assays and in vivo studies using mouse models to evaluate the efficacy of Indikizumab.

Results: Indikizumab demonstrated a high binding affinity (K_D=27.2 pM) and specificity for IL-17A, with comparable potency to Secukinumab. In cell-based neutralization assays, Indikizumab effectively neutralized the effects of IL-17A and demonstrated a statistically significant reduction in plasma KC (Keratinocyte) levels in a mouse model. In imiquimod-induced psoriasis mouse model, Indikizumab showed potential in reducing the psoriasis index.

Conclusion: Indikizumab represents a promising therapeutic option for inflammatory indications with its high binding affinity, specificity for IL-17A, and effectiveness in neutralizing IL-17A effects in vivo.

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新型抗IL-17A抗体Indikizumab的初步研究和疗效测定

目的：该研究旨在开发一种新型人源化抗IL-17A单克隆抗体（mAb）--Indikizumab，并确定其特性，以用于银屑病、银屑病关节炎、类风湿性关节炎和强直性脊柱炎等炎症适应症的潜在治疗：研究涉及 IL-17 异构体的纯化、表位图绘制、亲和力排序以及抗 IL-17 抗体的比较结合评估。研究还包括基于细胞的中和试验和使用小鼠模型的体内研究，以评估英迪库单抗的疗效：结果：Indikizumab对IL-17A具有很高的结合亲和力（KD=27.2 pM）和特异性，效力与Secukinumab相当。在基于细胞的中和试验中，Indikizumab能有效中和IL-17A的作用，并在小鼠模型中显著降低血浆KC（角质细胞）水平。在咪喹莫特诱导的银屑病小鼠模型中，Indikizumab显示出降低银屑病指数的潜力：结论：Indikizumab与IL-17A的结合亲和力高、特异性强，而且能有效中和IL-17A在体内的作用，因此是治疗炎症适应症的一种很有前景的选择。

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