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 Suppl. 1991 Jun;14:71-3.
The potential of mouse monoclonal antibodies raised against the human small cell lung cancer (SCLC) cell line SW2 to form active immunotoxins was evaluated using an indirect assay of immunotoxin cytotoxicity. Monoclonal antibodies recognising different SCLC-associated antigens, designated as cluster w4 and cluster 5A antibodies by the First International Workshop on SCLC Antigens, mediated the cytotoxic action of a screening agent made by linking ricin A chain to sheep anti-mouse IgG Fab' fragment. In contrast, monoclonal antibodies belonging to cluster 1 gave no significant cytotoxic effects in conjunction with the screening agent. Immunotoxins made by the direct chemical conjugation of ricin A chain to SWA11 (cluster w4) and SWA20 (cluster 5A) both exhibited selective toxic effects upon the SW2 cell line in tissue culture, inhibiting the incorporation of 3H-leucine by 50% at a concentration (IC50) of approximately 3 x 10(-10) M. An immunotoxin made with SEN36 (cluster 1) was much less potent with an IC50 greater than 1 x 10(-8) M.
利用免疫毒素细胞毒性的间接检测方法，评估了针对人小细胞肺癌（SCLC）细胞系SW2产生的小鼠单克隆抗体形成活性免疫毒素的潜力。第一届SCLC抗原国际研讨会将识别不同SCLC相关抗原的单克隆抗体指定为w4簇和5A簇抗体，这些抗体介导了通过将蓖麻毒素A链与羊抗小鼠IgG Fab'片段连接而成的筛选剂的细胞毒性作用。相比之下，属于1簇的单克隆抗体与筛选剂联合使用时未产生明显的细胞毒性作用。通过将蓖麻毒素A链直接化学偶联到SWA11（w4簇）和SWA20（5A簇）制成的免疫毒素在组织培养中均对SW2细胞系表现出选择性毒性作用，在浓度（IC50）约为3×10⁻¹⁰ M时抑制3H-亮氨酸掺入达50%。用SEN36（1簇）制成的免疫毒素效力低得多，IC50大于1×10⁻⁸ M。
