Hellström I, Horn D, Linsley P, Brown J P, Brankovan V, Hellström K E
Cancer Res. 1986 Aug;46(8):3917-23.
We have evaluated approximately 10,000 monoclonal antibodies (MoAb) resulting from 25 hybridizations of spleen cells from mice immunized with cells from human non-small cell lung carcinoma or fetal lung. The spleen cells were hybridized with NS-1 myeloma cells, and the resulting hybridomas were screened for production of MoAb to non-small cell lung carcinoma by binding assays with either cell extracts or cells growing in culture, followed by immunohistology on frozen sections. Fourteen MoAb had relative specificity for non-small cell lung carcinoma versus normal tissues. Three of these MoAb (L3, L6, L17) also reacted with most carcinomas of the breast and colon, and two MoAb (L20 and L22) reacted with the four samples of small cell lung carcinoma tested. No MoAb defined an antigen of absolute tumor specificity, and no MoAb reacted substantially more with adenocarcinoma than squamous cell carcinoma of the lung (or vice versa). Five MoAb were Ig G1, two were Ig G2a, and the remaining seven were Ig M. Seven MoAb (L5, L6, L15, L17, L20, L22, L23) could bind to the cell surface. Three MoAb (L6, L15, L17) defined carbohydrate antigens, and three (L3, L5, L20) were to protein antigens, while the antigens to which the remaining MoAb are directed have not been identified. Six MoAb could bind to tumor cells in Carnoy-fixed paraffin-embedded sections. An intercellular variability in antigen expression was detected with all 14 MoAb. At least two of the MoAb, L6 and L20, are good candidates for preclinical testing in view of their high level of tumor selectivity, as shown by both immunohistology and binding assays with living cells.
我们评估了约10000种单克隆抗体(MoAb),这些抗体来自用人类非小细胞肺癌或胎儿肺细胞免疫的小鼠脾脏细胞进行的25次杂交。将脾脏细胞与NS-1骨髓瘤细胞杂交,然后通过与细胞提取物或培养中的细胞进行结合试验,筛选产生针对非小细胞肺癌的MoAb的杂交瘤,随后对冰冻切片进行免疫组织学检查。14种MoAb对非小细胞肺癌与正常组织具有相对特异性。其中3种MoAb(L3、L6、L17)也与大多数乳腺癌和结肠癌发生反应,2种MoAb(L20和L22)与所检测的4例小细胞肺癌样本发生反应。没有MoAb定义出绝对肿瘤特异性抗原,并且没有MoAb与肺腺癌的反应明显多于肺鳞状细胞癌(反之亦然)。5种MoAb为Ig G1,2种为Ig G2a,其余7种为Ig M。7种MoAb(L5、L6、L15、L17、L20、L22、L23)可结合细胞表面。3种MoAb(L6、L15、L17)定义了碳水化合物抗原,3种(L3、L5、L20)针对蛋白质抗原,而其余MoAb所针对的抗原尚未确定。6种MoAb可结合卡诺固定石蜡包埋切片中的肿瘤细胞。使用所有14种MoAb均检测到抗原表达的细胞间变异性。鉴于免疫组织学和活细胞结合试验均显示其具有高水平的肿瘤选择性,至少2种MoAb,即L6和L20,是临床前测试的良好候选者。