Staerz U D, Bevan M J
Proc Natl Acad Sci U S A. 1986 Mar;83(5):1453-7. doi: 10.1073/pnas.83.5.1453.
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 cell lines may have application in the therapeutic targeting of tumors or sites of viral infections for attack by T cells.
先前的研究表明,单克隆抗体的异源缀合物(其中一种组分抗体针对T细胞受体,另一种针对任何选定部位)可以使效应T细胞聚焦于靶向部位发挥作用。我们在此报告一种杂交杂交瘤细胞系H1.10.1.6的产生,该细胞系分泌大量IgG2a类双特异性杂交抗体,可聚焦T细胞活性。二次融合的亲本杂交瘤细胞系是F23.1(分泌针对大多数小鼠品系T细胞受体上同种异型决定簇的特异性抗体)和19E12(分泌抗Thy-1.1抗体)。通过羟基磷灰石色谱法对双特异性杂交抗体进行部分纯化,并通过等电聚焦进行表征。它能有效地靶向表达Thy-1.1的肿瘤细胞,使其在体外被F23.1受体阳性的细胞毒性T细胞克隆裂解。由杂交杂交瘤细胞系产生的此类杂交抗体可能在肿瘤或病毒感染部位的治疗性靶向中发挥作用,以使T细胞对其进行攻击。