抗CD3-表皮生长因子受体标记的树突状细胞-细胞因子诱导的杀伤细胞对肺癌小鼠免疫治疗的研究  

Preparation of anti - CD3 - epidermal growth factor receptor bispecific antibody - labeled dendritic cells- cytokine induced killer cells and immunotherapy study of it on lung cancer mice

作　　者：吴中杰 张雁飞 胡奕 蒋伟 Wu Zhongjie;Zhang Yanfei;Hu Yi;Jiang Wei(Department of Thoracic Surgery,Jiaxing First Hospital of Zhejiang Province,Jiaxing 314001,China;Department of Thoracic Surgery,Zhongshan Hospital Affiliated of Fudan Universi-ty,Shanghai 200032,China)

机构地区：[1]嘉兴市第一医院胸外科,314001 [2]复旦大学附属中山医院胸外科,上海200032

出　　处：《中华实验外科杂志》2018年第9期1697-1699,共3页Chinese Journal of Experimental Surgery

基　　金：嘉兴市科技计划项目（2016AY23040）

摘　　要：目的通过抗CD3／抗表皮生长因子受体（EGFR）双特异性抗体标记树突状细胞-细胞因子诱导的杀伤细胞（DC-CIK）免疫细胞的制备、鉴定及检测体内外杀伤肺癌细胞的能力。方法用化学耦联法将抗CD3单克隆抗体和抗EGFR单克隆抗体耦联，并标记于DC-CIK细胞表面，进行鉴定；体外检测其对A549肺癌细胞杀伤能力，体内检测其对肺癌裸小鼠的抑瘤能力。结果抗CD3／抗EGFR双特异性抗体标记DC-CIK免疫细胞制备成功，双标记的DC-CIK细胞对EGFR阳性肺癌A549肿瘤细胞的杀伤率[（86．47±4．82）％]高于DC-CIK细胞[（51．23±0．81）％]（F=41．432，P=0．003）。在肺癌裸小鼠治疗40d时，DC-CIK＋双特异性抗体对肿瘤相对增殖率[（80．47±7．69）％]低于溶媒组[（97．68±10．56）％]与普通DC-CIK细胞组[（101．24±9．62）％]（F=5．187，P=0．037；F=5．396，P=0．034），而DC-CIK组的肿瘤体积与溶媒组比较差异无统计学意义（F=1．045，P=0．365）。结论用抗CD3一EGFR双特异性抗体标记的DC-CIK免疫细胞对A549肺癌细胞具有强的杀伤能力，体内条件下对肺癌可能有治疗作用。Objective To study the preparation, identification, detection the ability of killing lung cancer cells of anti - CD3/anti - epidermal growth factor receptor （EGFR） bispecific antibody - labeled dendritic cells - cytokine induced killer cells （ DC - CIK） immune ceils, and to provide experimental guid- ance for the clinical application of this method in the treatment of lung cancer. Methods Anti - CD3 monoclonal antibody and anti -EGFR monoclonal antibody were conjugated by chemical coupling method and labeled on the surface of DC - CIK cells. The anti - CD3/anti - EGFR bispecific antibody - labeled DC - CIK immune cells was identified and detected the ability of killing A549 lung cancer cells in vitro and inhibiting lung cancer tumor growth in vivo. Results Anti - CD3/anti - EGFR bispecific antibody - la- beled DC - CIK immune cells established successfully. The anti - tumor activity of the anti - CD3/anti - EGFR group was （ 86.47 ± 4. 82 ） % , which was significantly higher than that in DC - CIK group [（51.23±0.81 ）%] （F=41.432, P=0.003）. When treated with lung cancer in nude mice for 40 days, The Tumor relative value rate of the anti - CD3/anti - EGFR group was （ 80. 47±7.69） %, which was significantly lower than that in DC - CIK group [ （ 101.24±9. 62 ） % ] （ F = 5. 187, P = 0. 037 ; F = 5. 396, P =0. 034）. There was no difference in treMor volume compared DC -CIK group and the vehicle group （F = 1. 045, P = O. 365）. Conclusion DC - CIK immunized ceils labeled with anti - CD3 - EGFR bispecific antibody has strong killing capacity on A549 lung cancer cells, and a powerful curative effect on lung cancer in vivo.

关 键 词：双特异性抗体 树突状细胞-细胞因子诱导的杀伤细胞 表皮生长因子受体 肺癌 

分 类 号：R734.2[医药卫生—肿瘤]