2D4, a humanized monoclonal antibody targeting CD132, is a promising treatment for systemic lupus erythematosus.

Nov 18, 2024

Experts: Huiqi Yin,Liming Li,Xiwei Feng,Zijun Wang,Meiling Zheng,Junpeng Zhao,Xinyu Fan,Wei Wu,Lingyu Gao,Yijing Zhan,Ming Zhao,Qianjin Lu

Current therapies for systemic lupus erythematosus that target a particular factor or cell type exhibit limited effectiveness. To address this limitation, our focus was on CD132, a subunit common to six inflammatory factor receptors implicated in SLE. Our study revealed heightened CD132 expression in SLE patients’ lymphocytes, contributing to the production of pro-inflammatory cytokines and immunoglobulins. We developed a novel humanized anti-CD132 monoclonal antibody, named as 2D4. 2D4 efficiently blocked IL-21 and IL-15, with limited effectiveness against IL-2, thereby suppressing T and B cells without disrupting immune tolerance. In the mouse immunization model, 2D4 virtually inhibited T cell-dependent, antigen-specific B-cell response. In lupus murine models, 2D4 mitigated inflammation by suppressing multiple pro-inflammatory cytokines and anti-dsDNA antibody titers, also diminishing proteinuria and glomerulonephritis. Compared to Belimumab, 2D4 exhibited superior efficacy in ameliorating the inflammatory state and preserving renal function. Moreover, 2D4 exhibited the ability to inhibit the production of pro-inflammatory factors and autoantibodies in PBMCs from individuals with SLE, highlighting its therapeutic potential for SLE individuals. Potent, 2D4 has the potential to significantly improve clinical outcomes in SLE and other complex autoimmune disorders.
© 2024. The Author(s).

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ABOUT THE EXPERTS

Huiqi Yin,Liming Li,Xiwei Feng,Zijun Wang,Meiling Zheng,Junpeng Zhao,Xinyu Fan,Wei Wu,Lingyu Gao,Yijing Zhan,Ming Zhao,Qianjin Lu

Huiqi Yin

Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.

Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Liming Li

Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.

Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Xiwei Feng

Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.

Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Zijun Wang

Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, China.

Meiling Zheng

Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.

Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Junpeng Zhao

Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.

Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Xinyu Fan

Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.

Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Wei Wu

Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.

Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Lingyu Gao

Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.

Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Yijing Zhan

Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.

Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Ming Zhao

Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China. zhaoming301@pumcderm.cams.cn.

Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China. zhaoming301@pumcderm.cams.cn.

Qianjin Lu

Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China. qianlu5860@pumcderm.cams.cn.

Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China. qianlu5860@pumcderm.cams.cn.