Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
PLoS One. 2012;7(3):e33009. doi: 10.1371/journal.pone.0033009. Epub 2012 Mar 30.
Monoclonal antibody (McAb) is the key tool for cancer immunodiagnosis and immunotherapy. McAb-based immunotherapy that targets tumor antigens has had great achivement. In this study, a cell clone which kept secreting high-titer IgG1-type McAb named NJ001 against human non-small cell lung cancer (NSCLC) cells was obtained. The titer of purified NJ001 was 2×10(6). The antigen named SP70 of NSCLC specifically identified by NJ001 was proved to be a protein with the relative molecular mass (Mr) of 70 kDa. The results of immunohistochemical staining indicated that NJ001 could positively react to NSCLC, but weak positively or negatively react to human small-cell lung cancer (SCLC), pulmonary pseudotumor and other epithelial tumors. In soft agar assay, the colony formation efficiency in NJ001 groups decreased in a dose-dependent manner. For the concentration of 100 µg/ml, 200 µg/ml and 400 µg/ml, the inhibition ratio of colony formation was 23.4%, 62.5% and 100% respectively. Meanwhile, NJ001 caused significant reduction in tumor volume and tumor weight compared to control mice in lung cancer xenograft model. The tumor growth inhibition ratio in 200 µg, 400 µg and 800 µg NJ001 groups was 10.44%, 37.29% and 44.04%, respectively. NJ001 also led to cytomorphological changes and induced the apoptosis of human lung adenocarcinoma cell line SPC-A1 significantly. The newly developed NJ001 selectively reacted to NSCLC and exhibited anti-tumor activity both in vitro and in vivo. NJ001 is of great value concerning immunodiagnostics and immunotherapy for NSCLC and holds promise for further research regarding the mechanism underlying tumor progression of NSCLC.
单克隆抗体(McAb)是癌症免疫诊断和免疫治疗的关键工具。针对肿瘤抗原的 McAb 为基础的免疫治疗已经取得了巨大的成就。在这项研究中,获得了一种能够持续分泌高滴度 IgG1 型 McAb 的细胞克隆,该 McAb 针对人类非小细胞肺癌(NSCLC)细胞,命名为 NJ001。纯化后的 NJ001 的滴度为 2×10(6)。通过 NJ001 特异性识别的 NSCLC 抗原 SP70 被证明是一种相对分子质量(Mr)为 70 kDa 的蛋白质。免疫组织化学染色的结果表明,NJ001 可以与 NSCLC 阳性反应,但对人类小细胞肺癌(SCLC)、肺假性肿瘤和其他上皮肿瘤呈弱阳性或阴性反应。在软琼脂测定中,NJ001 组的集落形成效率呈剂量依赖性下降。在 100 µg/ml、200 µg/ml 和 400 µg/ml 浓度下,集落形成的抑制率分别为 23.4%、62.5%和 100%。同时,与对照组小鼠相比,在肺癌异种移植模型中,NJ001 导致肿瘤体积和重量显著减少。200 µg、400 µg 和 800 µg NJ001 组的肿瘤生长抑制率分别为 10.44%、37.29%和 44.04%。NJ001 还导致人肺腺癌细胞系 SPC-A1 的形态学变化和显著的凋亡。新开发的 NJ001 选择性地与 NSCLC 反应,并在体外和体内均显示出抗肿瘤活性。NJ001 对于 NSCLC 的免疫诊断和免疫治疗具有重要价值,为 NSCLC 肿瘤进展机制的进一步研究提供了前景。