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

被引:0
|
作者
Patra, Ashok Kumar [1 ,2 ]
Nayak, Shreenath [1 ]
Moharana, Anandita [1 ]
Ojha, Purusottam [1 ]
Das, Sanjeet Kumar [1 ]
Akhtar, Jabed [1 ]
Giri, Bishwaranjan [1 ]
Singh, Sujay [1 ]
机构
[1] Imgenex India Pvt Ltd, Prot Express Lab, E 5, Bhubaneswar, Odisha, India
[2] Imgenex India Pvt Ltd, Biol Dev, E 5, Bhubaneswar 751024, Odisha, India
来源
关键词
monoclonal antibody; neutralization assay; psoriasis; inflammation; keratinocyte; MONOCLONAL-ANTIBODY; T-CELL; PSORIASIS; IL-17; RECEPTOR; DISTINCT; SKIN; INTERLEUKIN-17; EPIDEMIOLOGY; OPTIMIZATION;
D O I
10.2147/BTT.S477752
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:257 / 271
页数:15
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