人源性荷三阴乳腺癌NOD/SCID小鼠模型建立及其免疫应答  

Establishment of a NOD/SCID mouse model with human immune reconstitution bearing human triple-negative breast cancer

作　　者：张翘楚[1] 李玺[1] 刘瑞磊[1] 姜华[1] 黄泽楠[1] 刘宇[1] 汤谧[1] 黄勇[1] 

机构地区：[1]中山大学附属第三医院甲状腺乳腺外科,广东广州510630

出　　处：《南方医科大学学报》2015年第1期56-61,共6页Journal of Southern Medical University

基　　金：中央高校基本科研业务费专项资金(09ykpy15)

摘　　要：目的建立具有人免疫学特征的NOD/SCID小鼠模型,并观察其对三阴乳腺癌的免疫应答。方法筛选无免疫渗漏NOD/SCID小鼠24只,分成4组,免疫重建组提前3 d腹腔注射250 mg/kg环磷酰胺（CTX）,后经腹腔注射健康人外周血单个核细胞（PBMC）同时背部皮下接种人三阴乳腺癌细胞MDA-MB-231;单纯免疫组只注射CTX及PBMC;单纯荷瘤组只接种MDA-MB-231;空白对照组不作任何处理。定期观察各组小鼠生物学及免疫学特征。结果免疫荷瘤组成瘤潜伏期（10~12 d）较单纯荷瘤组（8~10 d）延长,肿瘤生长速度减缓,第5周末肿瘤体积分别为1244.82±792.82 mm3和4308.77 mm3（P〈0.01）,生存率提高（P〈0.01）。接受免疫重建的小鼠外周血人Ig G于第2周即可测到,并逐渐上升,较未接受免疫重建小鼠差异有统计学意义（P〈0.01）。外周血中CD3＋细胞比例于第2周逐渐下降,但于第9周仍可测到。第9周小鼠脾脏细胞中CD3＋T细胞比例高达55.3%（免疫荷瘤组）及52.7%（单纯荷瘤组）。免疫荷瘤组小鼠脾指数9.64 mg/g明显高于单纯免疫组3.82±0.31 mg/g及空白对照组1.51±0.14 mg/g。结论成功构建稳定的具有人免疫学特征的NOD/SCID小鼠模型,并观察到其对三阴乳腺癌产生免疫应答,可为三阴乳腺癌免疫治疗研究提供较为理想的动物模型。Objective To establish a NOD/SCID mouse model with human immune reconstitution and observe its immune response to human triple- negative breast cancer xenograft. Methods Twenty- four NOD/SCID mice without immune leakage were subjected to cyclophosphamide（CTX） treatment 3 days prior to immune reconstitution with human peripheral blood mononuclear cell（PBMC） injection and subcutaneous transplantation of human triple- negative breast cancer MDA- MB- 231 cells, CTX treatment and PBMC injection without tumor cell transplantation, MDA- MB- 231 cell transplantation only, or no treatments. The tumor growth and immune responses of the mice were observed at regular intervals. Results Compared with the tumor- bearing mice, the tumor- bearing mice with immune reconstitution showed prolonged incubation period of tumor formation, slower tumor growth rate and increased survival rate. Human Ig G and CD3＋T cells were detected in the peripheral blood of the mice 1 week after human PBMC injection. The percentage of CD3＋T cells in the spleen cells was 55.3% at 9 weeks in tumor- bearing mice with immune reconstitution and 52.7% in tumor- bearing mice without immune reconstitution. The spleen index of the tumor- bearing mice with immune reconstitution was much higher than that in mice with only immune reconstitution and the control mice（9.64 vs 3.82±0.31 and 1.51±0.14 mg/g）. Conclusion A stable NOD/SCID mouse model with immune reconstitution has been established successfully, which shows immune responses to triple- negative breast cancer xenografts and allows studies of immunological therapy study of triple-negative breast cancer.

关 键 词：免疫重建 免疫治疗 NOD/SCID小鼠 三阴乳腺癌 

分 类 号：R737.9[医药卫生—肿瘤]