【作者】 喻明霞； 牛麟； 王晶； 尹丙娇； 姜小丹； 冯玮； 李卓娅；

【机构】 华中科技大学同济医学院基础医学院免疫学系；

【摘要】 目的:研究TM-TNF-α单克隆抗体体内外抗肿瘤的效应。方法:在体外实验中,用FACS检测乳腺癌细胞株MDA-MD-231的TM-TNF的表达;用经典ADCC和CDC方法检测C1单克隆抗体抗肿瘤效应。在体内实验中,采用常规的观测方法来检测C1 mA b对MDA-MD- 231乳腺癌细胞体内致瘤的影响。结果:在体外实验中,MDA-MD-231高表达TM-TNF-α达84.77%,C1 mAb可介导巨噬细胞对MDA-MD-231乳腺癌细胞产生明显的ADCC效应(P<0.001),C1 mAb介导补体对高表达TM-TNF的MDA-MD-231乳腺癌细胞具有明显杀伤,而对HUVEC细胞无影响。在体内实验中,C1 mAb可明显抑制肿瘤的生长(P<0.001),使肿瘤体积缩小(P<0.01),有3只小鼠的肿瘤完全消退。体内实验还证实在肿瘤生长至4周左右对照小鼠注射HBs mAb,小鼠均在其背部可见转移肿瘤,转移率分别为:57.1%和42.8%。而C1 mAb治疗则未见肿瘤转移。结论:TM-TNF单抗C1 mAb在体外介导表达TM-TNF肿瘤细胞的杀伤效应,在体内不仅能抑制肿瘤的生长,而且还可能抑制肿瘤的转移。更多还原

【Abstract】 Object:To research the anti-tumor effect of TM-TNF-αMcAb.Method:In in vitro experiment,detection of TM-TNF-αexpression on breast cancer cell line MDA-MD-231 by FACS; investigation of anti-tumor effect of C1 McAb by classical ADCC and CDC experiment.In in vivo experiment,investigation of effect of C1 McAb on tumor formation after transplantation of MDA-MD-231 into nude mouse by traditional experiment model.Result:There is a high expression rate of TM-TNF-αobserved on MDA-MD-231 cell line.In in vitro ADCC experiment, C1 McAb mediated macrophage cytotoxicity towards MDA-MD-231(P<0.001); In the CDC (complement dependent cytotoxicity) experiment,C1 McAb mediated complement cytotoxicity towards target MDA-MD-231 cells (P<0.001),while the irrelevant isotype control (HBs mAb) exhibited no ADCC or CDC effects.In in vivo experiment,C1 McAb significantly inhibits tumor growth (P<0.001) and reduces solid tumor size (P<0.001).3 nude mice underwent complete tumor regression.In vivo experiment indicates that there are visible metastatic tumors on the back of nude mice 4 weeks after transplantation in both control group and HBs mAb treatment group,with 57.1%and 42.8%metastasis rate respectively,while no metastatic tumor appears in the C1 McAb treatment group.Conclusion:In vitro,TM-TNF-a McAb mediates cytotoxicity against tumor cell In vivo,TM-TNF-αMcAb inhibits both the growth and metastasis of tumor cells.更多还原