HYBRID HYBRIDOMA PRODUCING A BISPECIFIC MONOCLONAL-ANTIBODY THAT CAN FOCUS EFFECTOR T-CELL ACTIVITY
HYBRID HYBRIDOMA PRODUCING A BISPECIFIC MONOCLONAL-ANTIBODY THAT CAN FOCUS EFFECTOR T-CELL ACTIVITY
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DOI：
10.1073/pnas.83.5.1453
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发表时间：
1986-03-01
影响因子：
11.1
通讯作者：
BEVAN, MJ
中科院分区：
文献类型：
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作者：
STAERZ, UD;BEVAN, MJ
先前的研究已经表明，其中一种组分抗体针对T细胞受体而另一种针对任何选定位点的单克隆抗体的杂合物可以使效应T细胞集中在靶向位点发挥功能。我们在这里报告生产的杂交瘤细胞系，H1.10.1.6，分泌大量的IgG 2a类的双特异性杂交抗体，可以集中T细胞活性。用于二次融合的亲本杂交瘤系是F23.1和19E 12，F23.1分泌对大多数小鼠品系的T细胞受体上的同种异型决定簇具有特异性的抗体，19E 12分泌抗Thy-1.1抗体。通过羟基磷灰石色谱法部分纯化双特异性杂交抗体，并通过等电聚焦进行表征。其有效靶向Thy-1.1表达肿瘤细胞，用于在体外被F23.1受体阳性细胞毒性T细胞克隆裂解。由杂交瘤细胞系产生的这种杂交抗体可应用于肿瘤或病毒感染部位的治疗靶向以供T细胞攻击。
Previous studies have shown that heteroconjugates of monoclonal antibodies in which one of the component antibodies is directed at the T-cell receptor and the other is directed against any chosen site can focus effector T cells to function at the targeted site. We report here the production of a hybrid hybridoma cell line, H1.10.1.6, which secretes large amounts of a bispecific hybrid antibody of the IgG2a class, that can focus T-cell activity. The parental hybridoma lines for the secondary fusion were F23.1, which secretes an antibody specific for an allotypic determinant on the T-cell receptor of most mouse strains, and 19E12, secreting an anti-Thy-1.1 antibody. The bispecific hybrid antibody was partially purified by hydroxylapatite chromatography and characterized by isoelectric focusing. It efficiently targets Thy-1.1-expressing tumor cells for lysis by F23.1 receptor-positive cytotoxic T-cell clones in vitro. Such hybrid antibodies produced by hybrid hybridoma cells lines may have application to the therapeutic targeting of tumors or sites of viral infections for attack by T-cells.