血卟啉衍生物-癌胚抗原单抗偶联物抗肿瘤特性的研究  

Study on the anti-tumor characteristics of HPD-anti-CEA monoclonal antibody conjugate

作　　者：刘建源[1] 鲁琰[2] 孔健[1] 

机构地区：[1]北京生物制品研究所 [2]北京大学医学部免疫学系

出　　处：《中华微生物学和免疫学杂志》2002年第1期88-91,共4页Chinese Journal of Microbiology and Immunology

摘　　要：目的　研究血卟啉衍生物 癌胚抗原单抗偶联物对表达癌胚抗原 (CEA)的肿瘤细胞的特异性杀伤作用。方法　将血卟啉衍生物 (HPD)与一种癌胚抗原单克隆抗体———C5 0单抗 ,通过碳二亚胺 (EDCI)偶联 ,制备HPD C5 0单抗偶联物。以表达CEA的SW1116细胞株和不表达CEA的Hep 2细胞株用MTT法进行体外肿瘤细胞的杀伤实验。结果　被鉴定偶联物的免疫活性与标准单抗差异无显著性 (P >0 .0 1)。偶联物较游离HPD对表达CEA的肿瘤细胞杀伤效果明显增强 (P <0 .0 5 ) ;显微镜下可见CEA阳性细胞死亡 ,对非表达CEA细胞 ,二者的作用无明显差异。对各摩尔比的偶联物进行测定 ,发现摩尔比为 6 6∶1时 ,杀伤效果最好 ,其HPD的半数杀伤浓度 <2 .2 μg/ml。结论　HPD C5Objective To study the specific killing effect of the HPD-anti-CEA monoclonal antibody immunoconjugate on the tumor cells that express CEA. Methods Hematoporphyrin derivative (HPD) was covalently coupled with a C50 McAb (against carcinoembryonic antigen, CEA) via [1-ethyl-3-(3-dimethyl-aminopropyl) carbodiimide hydrochloride] (EDCI) to yield conjugates with a molar ratio ranging from 55 to 100 mol of HPD per mol of C50 McAb. Antibody-mediated cytotoxicity was examined by the MTT test with SW1116, a CEA-positive cell line, and Hep-2, a CEA-negative cell line. Results (1) The conjugate showed similar immunoactivity as the native McAb did. (2) The four conjugates with different molar ratios were compared. The most effective one had a molar ratio of 66∶1. (3) Compared with the free HPD, the cytotoxicity of immunoconjugate showed more significant effect in killing the CEA-positive tumor cells, SW1116, than that of CEA-negative cells, Hep-2. For the effect on CEA-negative cells, no difference existed between the conjugate and free HPD. Conclusion HPD-C50 immunoconjugate can specifically kill CEA positive cells.

关 键 词：免疫偶联物 癌胚抗原单抗 血卟啉衍生物 PDT 抗肿瘤特性 免疫疗法 肿瘤 

分 类 号：R73-36[医药卫生—肿瘤]