کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8531002 | 1559728 | 2018 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Development of novel anti-CD19 antibody-drug conjugates for B-cell lymphoma treatment
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Development of novel anti-CD19 antibody-drug conjugates for B-cell lymphoma treatment Development of novel anti-CD19 antibody-drug conjugates for B-cell lymphoma treatment](/preview/png/8531002.png)
چکیده انگلیسی
B-cell lymphoma remains one of the most refractory tumors, and as such the development of novel treatment approaches, such as antibody-drug conjugates (ADCs), is required. To improve the stability and homogeneity of the ADCs, a humanized anti-CD19 monoclonal antibody (RC58) was developed in the present study. RC58 was based on the CD19 antigen as a potential molecular target of human B-cell lymphomas. RC58 has high CD19-binding affinity and can be internalized in CD19-positive cells through endocytosis. Furthermore, three types of RC58-based ADCs (ADC-1, ADC-2, and ADC-3) were generated using three kinds of Maleimide-PEG-based linkers with two different cytotoxins. The anti-tumor activities of the ADCs were confirmed by in vitro and in vivo experiments. The stability of the ADCs was also evaluated by incubation in human plasma for 10â¯days. In vitro experiments showed that the three ADCs had distinct inhibitory effects on several B-lymphoma cell lines. Meanwhile, a close correlation between efficacy and drug concentration was found in a nude mouse xenograft model of human B-cell lymphoma, after treatment with RC58-based ADCs. Our results suggest that ADC-1, with high efficiency, could be used as a potential therapeutic agent for human B-cell malignancies.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Immunopharmacology - Volume 62, September 2018, Pages 299-308
Journal: International Immunopharmacology - Volume 62, September 2018, Pages 299-308
نویسندگان
Zhuanglin Li, Mingxue Wang, Xuejing Yao, Huanzhao Li, Shenjun Li, Lina Liu, Deling Yu, Xue Li, Jianmin Fang, Changjiang Huang,