Patra Ashok Kumar, Nayak Shreenath, Moharana Anandita, Ojha Purusottam, Das Sanjeet Kumar, Akhtar Jabed, Giri Bishwaranjan, Singh Sujay
Protein Expression Lab, Imgenex India Pvt. Ltd. E-5, Bhubaneswar, Odisha, India.
Sujan Biologics, Inc., San Diego, California, USA.
Biologics. 2024 Sep 17;18:257-271. doi: 10.2147/BTT.S477752. eCollection 2024.
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.
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.
Indikizumab demonstrated a high binding affinity (K=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.
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.
本研究旨在开发并表征英迪珠单抗(Indikizumab),这是一种新型人源化抗白细胞介素 - 17A单克隆抗体(mAb),用于治疗银屑病、银屑病关节炎、类风湿关节炎和强直性脊柱炎等炎症性疾病。
该研究涉及白细胞介素 - 17亚型的纯化、表位定位、亲和力排序以及抗白细胞介素 - 17抗体的比较结合评估。研究还包括基于细胞的中和试验以及使用小鼠模型的体内研究,以评估英迪珠单抗的疗效。
英迪珠单抗对白细胞介素 - 17A表现出高结合亲和力(K = 27.2 pM)和特异性,效力与司库奇尤单抗相当。在基于细胞的中和试验中,英迪珠单抗有效中和了白细胞介素 - 17A的作用,并在小鼠模型中使血浆角质形成细胞趋化因子(KC)水平有统计学意义的降低。在咪喹莫特诱导的银屑病小鼠模型中,英迪珠单抗显示出降低银屑病指数的潜力。
英迪珠单抗因其高结合亲和力、对白细胞介素 - 17A的特异性以及在体内中和白细胞介素 - 17A作用的有效性,是炎症性疾病有前景的治疗选择。