A novel human anti-BAFF neutralizing monoclonal antibody derived from in vitro immunization
A novel human anti-BAFF neutralizing monoclonal antibody derived from in vitro immunization
复制标题
一种源自体外免疫的新型人抗 BAFF 中和单克隆抗体
DOI：
10.1016/j.biopha.2019.109430
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发表时间：
2019
影响因子：
7.5
通讯作者：
Tian Hong
中科院分区：
文献类型：
--
作者：
Tong Yue;Zhong Shengwei;Shan Zhenzhen;Yao Wenbing;Tian Hong
B细胞活化因子（BAFF）在B细胞发育和免疫应答的正常调节中起关键作用。其异常表达水平伴随着各种自身免疫性疾病的发生。因此，BAFF是治疗此类疾病的有效靶点。本文报道一种新的抗BAFF单克隆抗体。本文在改进体外免疫方法的基础上，以含非天然氨基酸对硝基苯丙氨酸（pNO_2 Phe）的重组BAFF为抗原，在体外诱导免疫应答。流式细胞仪分选浆细胞，并基于分选的浆细胞构建抗体库。利用噬菌体展示技术筛选高亲和力的抗原结合片段，获得抗BAFF人IgG。该抗体在体外和体内均能有效中和BAFF。我们认为，这种新型全长人源抗BAFF单克隆抗体是一种很有前途的治疗自身免疫性疾病的候选药物。
B-cell activating factor (BAFF) plays a key role in the normal regulation of B cell development and immune response. Its abnormal expression level is accompanied by the occurrence of various autoimmune diseases. Therefore, BAFF is an effective target for the treatment of such diseases. Here, we report a new anti-BAFF monoclonal antibody. Based on improvedin vitroimmunization method, we used a recombinant BAFF containing unnatural amino acidp-nitro-phenylalanine (pNO2Phe) as an antigen to trigger immune responsein vitro. The plasma cells were sorted by flow cytometry (FACS), and the antibody library was constructed based on the sorted plasma cells. The high affinity antigen-binding fragments were panned by phage display technology, and finally the anti-BAFF human IgG was obtained. The antibody demonstrated its ability to neutralize BAFF effectively bothin vitroandin vivo. We propose that this novel full-length human anti-BAFF monoclonal antibody is a promising therapeutic candidate for the treatment of autoimmune diseases.