Xu Xiao-Jun, Tang Yong-Min, Zhao Hai-Zhao, Guo Li, Wang Zhu-Jun
Division of Hematology/oncology and.
J Drug Target. 2014 Jul;22(6):488-97. doi: 10.3109/1061186X.2014.888072. Epub 2014 Feb 19.
Monoclonal antibody (mAb)-based targeted therapy is one of the most promising strategies to cure cancers. MAb ZCH-2B8a (2B8a) was a novel antibody generated in our laboratory, which presented potential to be a therapeutic agent for hematologic malignancies.
We investigated the reactivity profile of 2B8a mAb, identified the targeting antigen by proteomic and genetic approaches and evaluated its potential to exert tumor cell killing.
2B8a antigen was strictly expressed on lymph tissues and hematopoietic cells (mainly leukocytes), and was highly expressed on B-lineage leukemia cell lines and acute lymphoblastic leukemia (ALL) cells from patients. 2B8a antibody was quickly internalized into the target cells once binding to the antigen, but was capable of killing tumor cells through complement dependent cytotoxicity. To identify the 2B8a antigen, the proteins of Raji cells were immunoprecipitated with 2B8a antibody and analyzed by mass spectrometry, which indicated that coronin-1a was a potential candidate. Then, coronin-1a gene was cloned from Raji cells, inserted into plasmid pcDNA3.1 (+), and transfected into CHO cells. The intracellular 2B8a antigen level was significantly increased in the coronin-1a transfectant cell line.
2B8a mAb is a novel antibody targeting coronin-1a, which has the potential to be a therapeutic agent for B-lineage malignancies.
基于单克隆抗体（mAb）的靶向治疗是治疗癌症最有前景的策略之一。单克隆抗体ZCH-2B8a（2B8a）是我们实验室研发的一种新型抗体，具有成为血液系统恶性肿瘤治疗药物的潜力。
我们研究了2B8a单克隆抗体的反应谱，通过蛋白质组学和遗传学方法鉴定了靶向抗原，并评估了其杀伤肿瘤细胞的潜力。
2B8a抗原在淋巴组织和造血细胞（主要是白细胞）上严格表达，在B系白血病细胞系和患者的急性淋巴细胞白血病（ALL）细胞上高表达。2B8a抗体一旦与抗原结合，就能迅速内化到靶细胞中，但能够通过补体依赖性细胞毒性杀伤肿瘤细胞。为了鉴定2B8a抗原，用2B8a抗体对Raji细胞的蛋白质进行免疫沉淀并通过质谱分析，结果表明冠蛋白-1a是一个潜在的候选抗原。然后，从Raji细胞中克隆冠蛋白-1a基因，插入质粒pcDNA3.1（+），并转染到CHO细胞中。在冠蛋白-1a转染细胞系中，细胞内2B8a抗原水平显著升高。
2B8a单克隆抗体是一种靶向冠蛋白-1a的新型抗体，具有成为B系恶性肿瘤治疗药物的潜力。
