肺癌抑制性抗体及其抗原的鉴定  

A functional antibody targeting lung cancer and it′s antigen

作　　者：冉宇靓[1] 胡海[1] 陈立钊[1] 遇珑[1] 孙立新[1] 杨治华[1] 

机构地区：[1]中国医学科学院中国协和医科大学肿瘤研究所细胞生物学及分子生物学研究室,北京100021

出　　处：《中国肿瘤生物治疗杂志》2007年第2期110-114,共5页Chinese Journal of Cancer Biotherapy

基　　金：国家自然科学基金重点项目(No.30230150);国家重点基础研究发展规划(973计划)项目(No.2002CB513106)

摘　　要：目的:鉴定抑制肺癌细胞生长的功能性单克隆抗体1E2及其抗原,为治疗肺癌提供有潜力的靶向抗体治疗剂和分子靶位。方法:采用活细胞荧光、MTT细胞增殖实验、ELISA、动物体内治疗实验等方法检测鼠单克隆抗体1E2对人肺癌细胞增殖的抑制、单抗与癌细胞的结合部位、单抗的亚类和单抗对肺癌移植瘤的抑制,以Western blotting和MALDI TOF质谱方法鉴定该功能性单抗的抗原。结果:单抗1E2能够与肺癌细胞GLC82和NCI-H520的细胞膜结合,在体外能够明显抑制肺癌细胞的增殖。动物实验表明单抗1E2能够抑制肺癌移植瘤的生长,抑制率达49%。Western blotting显示其抗原相对分子质量约110000,质谱鉴定该抗原为氨甲酰磷酸合成酶(carbamoyl-phosphate synthetase1,CPS1)。结论:单抗1E2能够在体内外抑制肺癌的生长,具有成为肺癌靶向治疗剂的潜力。该抗体识别的抗原CPS1可表达于肺癌细胞的细胞膜,可能是一个肺癌靶向治疗的新靶位。Objective： To identify a functional monoclonal antibody 1E2 against lung cancer and its antigen, so as to provide a candidate antibody drug and molecule target for the anti-lung cancer therapy. Methods： The inhibition of the lung cancer cells, binding with tumor cells, isotypes, and inhibition of implanted tumor growth of 1 E2 monoclonal antibody were studied by immunofluorescence, ELISA, cell proliferation assay, and in vivo tumor treatment experiments. The corresponding antigen of 1 E2 was identified by Western blotting and MALDI-TOF mass spectrometry. Results： The 1 E2 antibody could recognize cell surface protein of lung cancer cell line GLC82 and HCI-H520 and obviously inhibited the lung cancer cell growth in vivo. Animal experiment revealed that 1 E2 antibody significantly inhibited lung tumor growth by 49%. Western blotting revealed that the molecular weight of the antigen of 1 E2 antibody was about 110 000. Mass fingerprint revealed this protein was carbamoyl-phosphate synthetase 1 （ CPS1 ）. Conclusion： 1 E2 monoclonal antibody can suppress lung tumor growth in vitro and in vivo; it might become a candidate drug for targeted lung cancer treatment. CPS1, the antigen of 1E2, locates on the membrane of lung cancer cells and it may become a novel molecule target for lung caner therapy.

关 键 词：肺癌 功能性单克隆抗体 抗原 靶位 靶向治疗 

分 类 号：R37[医药卫生—病原生物学]