靶向MSLN的CAR-NK-92细胞在胃癌中的抗肿瘤活性研究

Study on the antitumor activity of CAR-NK-92 cells targeting MSLN in gastric cancer

目的 探索靶向间皮素(MSLN)嵌合抗原受体改造的NK-92细胞在胃癌中的抗肿瘤活性.方法 构建靶向MSLN的二代嵌合抗原受体,利用慢病毒转染的方式将其导入NK-92细胞中得到MSLN CAR-NK-92细胞.通过免疫组化分析、流式细胞术及Western blot实验检测人胃癌肿瘤组织、人胃癌细胞中MSLN的表达情况.通过体外激活及体内肿瘤抑制实验研究CAR-NK-92细胞的特异性识别能力和抗肿瘤活性.结果 人胃癌肿瘤组织及肿瘤细胞中高表达MSLN.CAR-NK-92细胞可以特异性激活并裂解肿瘤细胞.与转染空载体的NK-92细胞比较,CAR-NK-92细胞可以明显抑制胃癌肿瘤的生长(P<0.01).结论 构建的靶向MSLN的CAR-NK-92在体内外都展现出显著的特异性杀伤MSLN+的胃癌细胞的活性,将有可能在胃癌的治疗中提供新的思路.

Objective To explore the antitumor activity of NK-92 cells modified with chimeric antigen receptor targeting mesothelin(MSLN)in gastric cancer.Methods The second generation chimeric antigen receptor targeting MSLN was constructed and transfected into NK-92 cells by lentivirus transfection to obtain MSLN CAR-NK-92 cells.The expression of MSLN in human gastric cancer tissues and human gastric cancer cells was detected by immunohistochemistry,flow cytometry and Western blot.The specific recognition ability and the anti-tumor activity of CAR-NK-92 cells were studied through in vitro activation and in vivo tumor inhibition experiments.Results MSLN was highly expressed in human gastric cancer tissue and tumor cells.CAR-NK-92 cells could specifically activate and lyse tumor cells.Compared with NK-92 cells transfected with an empty vector,CAR-NK-92 cells can significantly inhibited the growth of gastric cancer(P<0.01).Conclusion CAR-NK-92 targeting MSLN has shown significant activity in vivo and in vitro to kill gastric cancer cells specific to MSLN+,which may provide a new idea in the treatment of gastric cancer.