A bivalent single-chain Fv fragment against CD47 induces apoptosis for leukemic cells
A bivalent single-chain Fv fragment against CD47 induces apoptosis for leukemic cells
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DOI：
10.1016/j.bbrc.2004.01.128
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发表时间：
2004-03-19
影响因子：
3.1
通讯作者：
Tsuchiya, M
中科院分区：
文献类型：
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作者：
Kikuchi, Y;Uno, S;Tsuchiya, M
我们构建了小鼠单克隆抗体MABL的单链抗体片段（scFv），该片段特异性结合人CD47 （hCD47）并诱导白血病细胞凋亡。含有15个残基连接体的MABL抗体scFv （MABL scFv-15）可形成二聚体（M-r 50kDa）和单体（M-r 25kda）。MABL scFv-15二聚体和单体均对hCD47具有结合活性。MABL scFv-15二聚体在体外强烈诱导hcd47引入的小鼠白血病细胞凋亡，并在骨髓瘤移植小鼠模型中表现出抗肿瘤作用。而MABL scFv-15单体几乎没有表现出这些活性。这些结果有力地证明了CD47抗原通过MABL二聚体的两个抗原结合位点的连接是诱导细胞凋亡的必要条件。亲本MABL抗体由于在红细胞上表达CD47而引起血凝。有趣的是，MABL scFv-15二聚体没有引起血凝。这种诱导细胞凋亡的二聚体似乎是一种新的白血病治疗的主要候选物。(C) 2004爱思唯尔公司版权所有。
We constructed a single-chain antibody fragment (scFv) of murine monoclonal antibody, MABL, which specifically bound to human CD47 (hCD47) and induced apoptosis of the leukemic cells. The scFv of MABL antibody with a 15-residue linker (MABL scFv-15) formed both dimer (M-r 50kDa) and monomer (M-r 25 kDa). Both MABL scFv-15 dimer and monomer had binding activity for hCD47. MABL scFv-15 dimer strongly induced apoptosis of hCD47-introduced mouse leukemic cells in vitro and exhibited anti-tumor effect in a myeloma transplanted mice model. However, MABL scFv-15 monomer scarcely exhibited these activities. These results strongly demonstrate that the ligation of CD47 antigen by two antigen-binding sites of MABL dimer is needed for inducing apoptosis. The parent MABL antibody caused hemagglutination due to the CD47 expressed on erythrocytes. Interestingly, MABL scFv-15 dimer did not cause hemagglutination. This apoptosis-inducing dimer appears to be a lead candidate for novel leukemic therapy. (C) 2004 Elsevier Inc. All rights reserved.