Das C, Kulkarni P V, Constantinescu A, Antich P, Blattner F R, Tucker P W
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235.
Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9749-53. doi: 10.1073/pnas.89.20.9749.
We have produced a chimeric antibody (Ab) in which metallothionein, a well-characterized biological chelator of metals, was genetically fused to the F(ab') domain of the S107 Ab heavy chain. Coexpression with the Ab light chain that conveys specificity for the synthetic antigen phosphocholine was achieved in plasmacytoma cells. Metal- and antigen-binding domains of the Ab-metallothionein hybrid function with normal avidity and specificity. Ab-metallothionein can be efficiently loaded with 99mTc and used to specifically bind phosphocholine-haptenated cells in vitro or to localize plasma-cell ascites tumors in mice. The approach offers potential advantages for producing radiolabeled Ab for targeted radiotherapy and diagnostic imaging.
我们制备了一种嵌合抗体(Ab),其中金属硫蛋白(一种特性明确的金属生物螯合剂)与S107抗体重链的F(ab')结构域进行了基因融合。在浆细胞瘤细胞中实现了与对合成抗原磷酸胆碱具有特异性的抗体轻链的共表达。抗体-金属硫蛋白杂交体的金属结合域和抗原结合域具有正常的亲和力和特异性。抗体-金属硫蛋白可以有效地负载99mTc,并用于在体外特异性结合磷酸胆碱半抗原化的细胞,或在小鼠体内定位浆细胞腹水肿瘤。该方法为生产用于靶向放疗和诊断成像的放射性标记抗体提供了潜在优势。