A rationally designed CD19 monoclonal antibody-triptolide conjugate for the treatment of systemic lupus erythematosus
Tripterygium wilfordii Hook F (TWHF) is a traditional Chinese medicine widely used in the treatment of systemic lupus erythematosus (SLE), with triptolide (TP) as its main active ingredient. However, its side effects also induced by TP, especially hepatotoxicity and reproductive toxicity, largely li...
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2024-10-01
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| Series: | Acta Pharmaceutica Sinica B |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383524002557 |
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| author | Lai Wang Haoyuan Yin Jiao Jiang Qilin Li Changxing Gao Wenrui Li Bo Zhang Yue Xin Hongyang Li Ming Zhao Qianjin Lu |
| author_facet | Lai Wang Haoyuan Yin Jiao Jiang Qilin Li Changxing Gao Wenrui Li Bo Zhang Yue Xin Hongyang Li Ming Zhao Qianjin Lu |
| author_sort | Lai Wang |
| collection | DOAJ |
| description | Tripterygium wilfordii Hook F (TWHF) is a traditional Chinese medicine widely used in the treatment of systemic lupus erythematosus (SLE), with triptolide (TP) as its main active ingredient. However, its side effects also induced by TP, especially hepatotoxicity and reproductive toxicity, largely limit its application in a subset of patients. Monoclonal antibodies (mAbs) developed for the treatment of SLE that deplete B cells by targeting B cell-expressing antigens, such as CD19, have failed in clinical trials, partly due to their poor efficacy in consuming B cells. Here, we report the development of a rationally designed antibody‒drug conjugate (ADC), CD19 mAb-TP conjugate, to alleviate the side effects of TWHF and simultaneously improve the therapeutic efficacy of CD19 mAb. The CD19 mAb-TP conjugate, which was named ADC-TP, selectively depleted B cell subsets both in vitro and in vivo and effectively alleviated disease symptoms in mouse lupus models with enhanced therapeutic efficacy than CD19 mAb and fewer side effects than TP. Our present study proposes a CD19 mAb‒TP conjugate strategy to mitigate the toxicity of TWHF while also enhancing the therapeutical efficacy of CD19 mAbs for the treatment of SLE, providing a feasible method for improving the current agents used for treating SLE. |
| format | Article |
| id | doaj-art-1de8887387b14b4e86e1b223f6513efb |
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| issn | 2211-3835 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Elsevier |
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| series | Acta Pharmaceutica Sinica B |
| spelling | doaj-art-1de8887387b14b4e86e1b223f6513efb2025-08-20T02:11:37ZengElsevierActa Pharmaceutica Sinica B2211-38352024-10-0114104560457610.1016/j.apsb.2024.06.024A rationally designed CD19 monoclonal antibody-triptolide conjugate for the treatment of systemic lupus erythematosusLai Wang0Haoyuan Yin1Jiao Jiang2Qilin Li3Changxing Gao4Wenrui Li5Bo Zhang6Yue Xin7Hongyang Li8Ming Zhao9Qianjin Lu10Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China; Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing 210042, ChinaHospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China; Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing 210042, ChinaHospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China; Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing 210042, ChinaKey Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing 210042, China; Hunan Key Laboratory of Medical Epigenomics, the Second Xiangya Hospital, Central South University, Changsha 410011, ChinaHospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China; Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing 210042, ChinaHospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China; Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing 210042, ChinaHospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China; Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing 210042, ChinaHospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China; Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing 210042, ChinaHospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China; Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing 210042, ChinaHospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China; Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing 210042, China; Corresponding authors.Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China; Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing 210042, China; Corresponding authors.Tripterygium wilfordii Hook F (TWHF) is a traditional Chinese medicine widely used in the treatment of systemic lupus erythematosus (SLE), with triptolide (TP) as its main active ingredient. However, its side effects also induced by TP, especially hepatotoxicity and reproductive toxicity, largely limit its application in a subset of patients. Monoclonal antibodies (mAbs) developed for the treatment of SLE that deplete B cells by targeting B cell-expressing antigens, such as CD19, have failed in clinical trials, partly due to their poor efficacy in consuming B cells. Here, we report the development of a rationally designed antibody‒drug conjugate (ADC), CD19 mAb-TP conjugate, to alleviate the side effects of TWHF and simultaneously improve the therapeutic efficacy of CD19 mAb. The CD19 mAb-TP conjugate, which was named ADC-TP, selectively depleted B cell subsets both in vitro and in vivo and effectively alleviated disease symptoms in mouse lupus models with enhanced therapeutic efficacy than CD19 mAb and fewer side effects than TP. Our present study proposes a CD19 mAb‒TP conjugate strategy to mitigate the toxicity of TWHF while also enhancing the therapeutical efficacy of CD19 mAbs for the treatment of SLE, providing a feasible method for improving the current agents used for treating SLE.http://www.sciencedirect.com/science/article/pii/S2211383524002557Systemic lupus erythematosusTriptolideCD19Antibody‒drug conjugateB cellsReproductive toxicity |
| spellingShingle | Lai Wang Haoyuan Yin Jiao Jiang Qilin Li Changxing Gao Wenrui Li Bo Zhang Yue Xin Hongyang Li Ming Zhao Qianjin Lu A rationally designed CD19 monoclonal antibody-triptolide conjugate for the treatment of systemic lupus erythematosus Acta Pharmaceutica Sinica B Systemic lupus erythematosus Triptolide CD19 Antibody‒drug conjugate B cells Reproductive toxicity |
| title | A rationally designed CD19 monoclonal antibody-triptolide conjugate for the treatment of systemic lupus erythematosus |
| title_full | A rationally designed CD19 monoclonal antibody-triptolide conjugate for the treatment of systemic lupus erythematosus |
| title_fullStr | A rationally designed CD19 monoclonal antibody-triptolide conjugate for the treatment of systemic lupus erythematosus |
| title_full_unstemmed | A rationally designed CD19 monoclonal antibody-triptolide conjugate for the treatment of systemic lupus erythematosus |
| title_short | A rationally designed CD19 monoclonal antibody-triptolide conjugate for the treatment of systemic lupus erythematosus |
| title_sort | rationally designed cd19 monoclonal antibody triptolide conjugate for the treatment of systemic lupus erythematosus |
| topic | Systemic lupus erythematosus Triptolide CD19 Antibody‒drug conjugate B cells Reproductive toxicity |
| url | http://www.sciencedirect.com/science/article/pii/S2211383524002557 |
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