Haas C, Strauss G, Moldenhauer G, Iorio R M, Schirrmacher V
Division of Cellular Immunology, German Cancer Research Center, Heidelberg.
Clin Cancer Res. 1998 Mar;4(3):721-30.
The production and functional testing of two new bispecific (bs) hybrid antibodies [Abs; bs Ab hemagglutinin-neuraminidase (HN) x CD3 and bs Ab HN x CD28] designed for cancer vaccine modification are described. They allow distinct modifications of the human tumor cell vaccine ATV-NDV, an autologous tumor cell vaccine already modified by infection with Newcastle disease virus. The bs Abs use the viral HN molecule as a common foreign anchoring molecule for attachment to the tumor cells and allow the introduction of anti-CD3 or anti-CD28 T-cell-stimulatory molecules. The bs Abs attached to tumor target cells were able to cross-link CTL effector cells and up-regulate T-cell activation markers on autologous cancer patient-derived CD4 and CD8 T lymphocytes. This strategy of combining a cellular vaccine with a bs Ab is highly specific, quick, and economical and has broad-range applications. Five ng or less of target cell-bound bs Ab HN x CD28 were effective at augmenting T-cell-mediated antitumor cytotoxicity.
本文描述了两种新型双特异性（bs）杂交抗体[抗体；bs抗体血凝素-神经氨酸酶（HN）×CD3和bs抗体HN×CD28]的制备及功能测试，这两种抗体用于癌症疫苗修饰。它们可对人肿瘤细胞疫苗ATV-NDV进行不同修饰，ATV-NDV是一种已通过新城疫病毒感染进行修饰的自体肿瘤细胞疫苗。bs抗体利用病毒HN分子作为共同的外源锚定分子附着于肿瘤细胞，并可引入抗CD3或抗CD28 T细胞刺激分子。附着于肿瘤靶细胞的bs抗体能够交联CTL效应细胞，并上调自体癌症患者来源的CD4和CD8 T淋巴细胞上的T细胞活化标志物。将细胞疫苗与bs抗体相结合的这种策略具有高度特异性、快速且经济，具有广泛的应用。5 ng或更少的与靶细胞结合的bs抗体HN×CD28在增强T细胞介导的抗肿瘤细胞毒性方面有效。
