Hombach A, Mathas S, Jensen M, Tillmann T, Menges M, Diehl V, Kruis W, Pohl C
Klinik I für Innere Medizin, Universität zu Köln, Germany.
Anticancer Res. 1997 May-Jun;17(3C):2025-32.
The poor prognosis of advanced gastric carcinoma requires new therapeutic approaches. Among these, the specific activation of resting lymphocytes by bispecific antibodies may be promising. Here we describe the generation and function of a bispecific monoclonal antibody (bi-mab) with specificity for CD3 and for the tumor antigen CA72-4 (TAG72) on various gastrointestinal tumors. We established a hybrid/hybridoma by somatic fusion of two hybridoma lines secreting antibodies against CA72-4 and CD3 respectively and characterized its bimab OKT3/B72.3. In combination with costimulatory anti-CD28 antibodies resting peripheral lymphocytes could be activated specifically by bi-mab OKT3/B72.3 with T cell proliferation and IL-2 secretion. The bi-mab OKT3/B72.3 could also trigger the cytotoxicity of these T cells toward, CA72-4+ cells in vitro. Our results indicate, that bi-mab OKT3/B72.3 in combination with an anti-CD28 mab can redirect T cell cytotoxicity specifically against CA72-4+ tumor cells implicating a novel strategy for the specific immunotherapy of CA72-4+ tumors.
晚期胃癌的不良预后需要新的治疗方法。其中，双特异性抗体对静息淋巴细胞的特异性激活可能很有前景。在此，我们描述了一种对CD3以及各种胃肠道肿瘤上的肿瘤抗原CA72-4（TAG72）具有特异性的双特异性单克隆抗体（双抗）的产生及功能。我们通过分别分泌抗CA72-4和抗CD3抗体的两种杂交瘤细胞系的体细胞融合建立了一种杂交/杂交瘤，并对其双抗OKT3/B72.3进行了表征。与共刺激抗CD28抗体联合使用时，静息外周淋巴细胞可被双抗OKT3/B72.3特异性激活，导致T细胞增殖并分泌白细胞介素-2。双抗OKT3/B72.3在体外也可触发这些T细胞对CA72-4+细胞的细胞毒性。我们的结果表明，双抗OKT3/B72.3与抗CD28单抗联合使用可将T细胞细胞毒性特异性重定向至针对CA72-4+肿瘤细胞，这意味着CA72-4+肿瘤特异性免疫治疗的一种新策略。
