Wawrzynczak E J, Derbyshire E J, Henry R V, Parnell G D, Smith A, Waibel R, Stahel R A
Drug Targeting Laboratory, Institute of Cancer Research, Sutton, Surrey, UK.
Br J Cancer. 1990 Sep;62(3):410-4. doi: 10.1038/bjc.1990.308.
The potential of mouse monoclonal antibodies for recognising different antigens associated with human small cell lung cancer (SCLC) to form active immunotoxins was assessed by an indirect in vitro screening assay. The screening agent used was a conjugate made by linking ricin A chain to a sheep anti-mouse IgG Fab' fragment via a disulphide bond. The monoclonal antibodies SWA11 and SWA20 both mediated the toxic effects of ricin A chain against the HC12 classic SCLC cell line in dose-dependent fashion. The SWA11 antibody was the more effective; in combination with the screening agent at a concentration of 1 x 10(-7) M, it inhibited the incorporation of [3H] leucine into HC12 cells by 94% compared with only 44% inhibition in the case of SWA20. An immunotoxin made by the direct chemical conjugation of ricin A chain to SWA11 exhibited selective toxic effects upon HC12 cells in tissue culture inhibiting the incorporation of [3H] leucine by 50% at a concentration (IC50) of 6.2 x 10(-10) M and by 98% at 1 x 10(-7) M. SWA11-ricin A chain had an IC50 of 4.4 x 10(-10) M against the NCI-H69 classic SCLC cell line but showed no cytotoxic activity against the human lung adenocarcinoma cell line NCI-H23 at a concentration of 1 x 10(-8) M.
通过间接体外筛选试验评估了小鼠单克隆抗体识别与人类小细胞肺癌（SCLC）相关的不同抗原以形成活性免疫毒素的潜力。所使用的筛选剂是一种通过二硫键将蓖麻毒素A链与羊抗小鼠IgG Fab'片段连接而成的缀合物。单克隆抗体SWA11和SWA20均以剂量依赖方式介导蓖麻毒素A链对HC12经典SCLC细胞系的毒性作用。SWA11抗体更有效；与浓度为1×10（-7）M的筛选剂联合使用时，它抑制[3H]亮氨酸掺入HC12细胞的比例为94%，而SWA20仅为44%。通过将蓖麻毒素A链与SWA11直接化学偶联制备的免疫毒素在组织培养中对HC12细胞表现出选择性毒性作用，在浓度（IC50）为6.2×10（-10）M时抑制[3H]亮氨酸掺入的比例为50%，在1×10（-7）M时为98%。SWA11-蓖麻毒素A链对NCI-H69经典SCLC细胞系的IC50为4.4×10（-10）M，但在浓度为1×10（-8）M时对人肺腺癌细胞系NCI-H23无细胞毒性活性。
