1. Preliminary Investigation and Therapeutic Efficacy Determination of a Novel Anti-IL-17A Antibody, Indikizumab
- Author
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Patra AK, Nayak S, Moharana A, Ojha P, Das SK, Akhtar J, Giri B, and Singh S
- Subjects
monoclonal antibody ,neutralization assay ,psoriasis ,inflammation. keratinocyte. ,Medicine (General) ,R5-920 - Abstract
Ashok Kumar Patra,1 Shreenath Nayak,1 Anandita Moharana,1 Purusottam Ojha,1 Sanjeet Kumar Das,1 Jabed Akhtar,1 Bishwaranjan Giri,1 Sujay Singh1,2 1Protein Expression Lab, Imgenex India Pvt. Ltd. E-5, Bhubaneswar, Odisha, India; 2Sujan Biologics, Inc., San Diego, California, USACorrespondence: Ashok Kumar Patra, Director, Biologics Development, Imgenex India Pvt. Ltd, E 5, Infocity, Technology Corridor, Chandaka Industrial Area, Bhubaneswar, Odisha, India, 751024, Email apatra@imgeneindia.comPurpose: 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 (KD=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.Keywords: monoclonal antibody, neutralization assay, psoriasis, inflammation. keratinocyte
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- 2024