Azuma A
Department of Clinical Pathology, Nippon Medical School, Tokyo, Japan.
Nihon Ika Daigaku Zasshi. 1991 Dec;58(6):663-72. doi: 10.1272/jnms1923.58.663.
In this study, we show that bispecific hetero-F(ab')2 enhances cytolytic activity in human lymphokine activated killer (LAK) cells derived from peripheral blood mononuclear cells against human small cell lung cancer (SCLC) cell lines. We used two types of bispecific F(ab')2 (anti-CD3-LU246mAb, anti-CD16-LU246mAb) which play different roles in the enhancement of cytolytic activity in LAK cells against the human SCLC cell lines N231, H69 and Lu135. Anti-CD3 Fab' or anti-CD16 Fab' were coupled with LU246 Fab' that recognized the antigen on human SCLC cells for reproducing bispecific F(ab')2. Anti-CD16 (3G8) Fab' conjugated with LU246 Fab' targeted NK-LAK cells to SCLC cells to mediate cytolysis, but NK-LAK cells induced by LGL-enriched fraction did not display enhanced cytotoxicity even when bispecific antibody was used in 51Cr release assay. Anti-CD3 (OKT3) Fab' conjugated with LU246 Fab' cross-linked T-LAK cells to SCLC cells activated T-LAK cells through the CD3 complex, and enhanced the cytolytic activity of T-LAK cells against SCLC lines. Although OKT3-LU246 F(ab')2 was not so potent in enhancing cytolytic activity in 51Cr release assay, it played a greater role in enhancing the inhibitory effect on tumor growth than 3G8-LU246 F(ab')2 in human tumor clonogenic assay and in vivo tumor neutralization assay. In addition, the enhancement of target cell lysis by bispecific antibodies was generally more potent than antibody dependent cellular cytotoxicity (ADCC) using LU246 monoclonal antibody.
在本研究中，我们发现双特异性异源F(ab')2可增强源自外周血单个核细胞的人淋巴因子激活的杀伤细胞（LAK细胞）对人小细胞肺癌（SCLC）细胞系的细胞溶解活性。我们使用了两种双特异性F(ab')2（抗CD3-LU246单克隆抗体、抗CD16-LU246单克隆抗体），它们在增强LAK细胞对人SCLC细胞系N231、H69和Lu135的细胞溶解活性中发挥不同作用。抗CD3 Fab'或抗CD16 Fab'与识别人类SCLC细胞上抗原的LU246 Fab'偶联，以制备双特异性F(ab')2。与LU246 Fab'偶联的抗CD16（3G8）Fab'将NK-LAK细胞靶向SCLC细胞以介导细胞溶解，但即使在51Cr释放试验中使用双特异性抗体，由富含大颗粒淋巴细胞（LGL）的组分诱导的NK-LAK细胞也未显示出增强的细胞毒性。与LU246 Fab'偶联的抗CD3（OKT3）Fab'使T-LAK细胞与SCLC细胞交联，通过CD3复合物激活T-LAK细胞，并增强T-LAK细胞对SCLC细胞系的细胞溶解活性。尽管OKT3-LU246 F(ab')2在51Cr释放试验中增强细胞溶解活性方面效果不那么显著，但在人肿瘤克隆形成试验和体内肿瘤中和试验中，它在增强对肿瘤生长的抑制作用方面比3G8-LU246 F(ab')2发挥了更大作用。此外，双特异性抗体对靶细胞裂解的增强作用通常比使用LU246单克隆抗体的抗体依赖性细胞毒性（ADCC）更强。
