Hombach A, Tillmann T, Jensen M, Heuser C, Sircar R, Diehl V, Kruis W, Pohl C
Klinik I für Innere Medizin der Universität zu Köln, Germany.
J Immunother. 1997 Sep;20(5):325-33. doi: 10.1097/00002371-199709000-00001.
Specific activation of resting lymphocytes for tumor targeting can be achieved by bispecific monoclonal antibodies (bi-mAb) with specificity for tumor antigens and T-cell-activating antigens, respectively, in combination with a costimulatory anti-CD28 antibody. We describe the generation and function of a bi-mAb with specificity for CD3 and for the tumor antigen CA19-9. The bi-mAb OKT3/NSI19-9 was generated by somatic fusion of two hybridoma lines secreting antibodies against CA19-9 and CD3, respectively. A hybrid/hybridoma was established, and its bi-mAb was characterized. In combination with a costimulatory anti-CD28 mAb resting peripheral lymphocytes could be activated specifically with T-cell proliferation and secretion of high amounts of interferon-gamma. On specific T-cell activation, bi-mAb OKT3/NSI19-9 could also redirect the cytotoxic effects of these T cells toward CA19-9+ tumor cells in vitro. Our results indicate that specific activation of resting T cells with bi-mAb OKT3/NSI19-9 in combination with an anti-CD28 mAb can activate resting T cells specifically and leads to antigen-dependent bi-mAb-mediated cytotoxicity against CA19-9+ target cells. This approach may offer new perspectives for the specific immunotherapy of CA19-9+ tumors.
通过分别对肿瘤抗原和T细胞激活抗原具有特异性的双特异性单克隆抗体（双抗），结合共刺激抗CD28抗体，可实现静止淋巴细胞针对肿瘤的特异性激活。我们描述了一种对CD3和肿瘤抗原CA19-9具有特异性的双抗的产生及其功能。双抗OKT3/NSI19-9是通过分别分泌抗CA19-9和抗CD3抗体的两种杂交瘤细胞系进行体细胞融合产生的。建立了一种杂交/杂交瘤，并对其双抗进行了表征。与共刺激抗CD28单克隆抗体联合使用时，静止外周淋巴细胞可被特异性激活，T细胞增殖并分泌大量干扰素-γ。在特异性T细胞激活后，双抗OKT3/NSI19-9还可在体外将这些T细胞的细胞毒性作用重定向至CA19-9+肿瘤细胞。我们的结果表明，双抗OKT3/NSI19-9与抗CD28单克隆抗体联合使用可特异性激活静止T细胞，并导致抗原依赖性双抗介导的针对CA19-9+靶细胞的细胞毒性。这种方法可能为CA19-9+肿瘤的特异性免疫治疗提供新的视角。
