A fully human connective tissue growth factor blocking monoclonal antibody ameliorates experimental rheumatoid arthritis through inhibiting angiogenesis.
A fully human connective tissue growth factor blocking monoclonal antibody ameliorates experimental rheumatoid arthritis through inhibiting angiogenesis.
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DOI：
10.1186/s12896-023-00776-8
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发表时间：
2023-03-03
影响因子：
3.5
通讯作者：
Yang, Xinyu
中科院分区：
文献类型：
--
作者：
Qin, Yang;Wu, Gan;Jin, Jiayi;Wang, Hao;Zhang, Jiani;Liu, Li;Zhao, Heping;Wang, Jianguang;Yang, Xinyu
结缔组织生长因子（CTGF）通过促进血管生成在类风湿性关节炎（RA）的发病机制中发挥着关键作用，是 RA 治疗的一个有前途的治疗靶点。在此，我们通过噬菌体展示技术产生了全人源CTGF阻断单克隆抗体（mAb）。通过筛选全人噬菌体展示文库，分离得到与人CTGF具有高亲和力的单链片段变量（scFv）。我们进行了亲和力成熟以提高其对 CTGF 的亲和力，并将其重建为全长 IgG1 格式以进一步优化。表面等离子共振 (SPR) 数据显示，全长抗体 IgG mut-B2 与 CTGF 结合，解离常数 (KD) 低至 0.782 nM。在胶原诱导关节炎 (CIA) 小鼠中，IgG mut-B2 以剂量依赖性方式减轻关节炎并降低促炎细胞因子的水平。此外，我们证实 CTGF 的 TSP-1 结构域对于相互作用至关重要。此外，Transwell实验、管形成实验和绒毛尿囊膜（CAM）实验的结果表明IgG mut-B2可以有效抑制血管生成。拮抗CTGF的全人源单克隆抗体可有效缓解CIA小鼠的关节炎，其机制与CTGF的TSP-1结构域密切相关。在线版本包含可在 10.1186/s12896-023-00776-8 获取的补充材料。
Connective tissue growth factor (CTGF) plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA) by facilitating angiogenesis and is a promising therapeutic target for RA treatment. Herein, we generated a fully human CTGF blocking monoclonal antibody (mAb) through phage display technology. A single-chain fragment variable (scFv) with a high affinity to human CTGF was isolated through screening a fully human phage display library. We carried out affinity maturation to elevate its affinity for CTGF and reconstructed it into a full-length IgG1 format for further optimization. Surface plasmon resonance (SPR) data showed that full-length antibody IgG mut-B2 bound to CTGF with a dissociation constant (KD) as low as 0.782 nM. In the collagen-induced arthritis (CIA) mice, IgG mut-B2 alleviated arthritis and decreased the level of pro-inflammatory cytokines in a dose-dependent manner. Furthermore, we confirmed that the TSP-1 domain of CTGF is essential for the interaction. Additionally, the results of Transwell assays, tube formation experiments, and chorioallantoic membrane (CAM) assays showed that IgG mut-B2 could effectively inhibit angiogenesis. The fully human mAb that antagonizes CTGF could effectively alleviate arthritis in CIA mice, and its mechanism is tightly associated with the TSP-1 domain of CTGF. The online version contains supplementary material available at 10.1186/s12896-023-00776-8.
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影响因子：
14.9
作者：
Dunbar J;Krawczyk K;Leem J;Marks C;Nowak J;Regep C;Georges G;Kelm S;Popovic B;Deane CM
通讯作者：
Deane CM
DOI：
10.1007/978-1-59745-554-1_15
发表时间：
2009
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Ho, Mitchell;Pastan, Ira
通讯作者：
Pastan, Ira
DOI：
10.1083/jcb.114.6.1285
发表时间：
1991-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bradham DM;Igarashi A;Potter RL;Grotendorst GR
通讯作者：
Grotendorst GR
影响因子：
56.9
作者：
Kolfschoten, Marijn van der Neut;Schuurman, Janine;Parren, Paul W. H. I.
通讯作者：
Parren, Paul W. H. I.
影响因子：
27.4
作者：
Burmester GR;Lin Y;Patel R;van Adelsberg J;Mangan EK;Graham NM;van Hoogstraten H;Bauer D;Ignacio Vargas J;Lee EB
通讯作者：
Lee EB