靶向间皮素的CAR-NK-92对卵巢癌的作用研究

Effect of CAR-NK-92 targeting MSLN on ovarian cancer

目的探讨靶向间皮素(MSLN)的嵌合抗原受体NK-92(CAR-NK-92)细胞对卵巢癌细胞的杀伤作用。方法通过免疫组化分析法和免疫荧光法分别检测原发性卵巢癌组织和卵巢癌细胞系MSLN的表达情况。使用慢病毒转染的方法构建靶向MSLN的CAR-NK-92细胞,流式细胞术检测其转染效率,并在体内和体外验证CAR-NK-92对卵巢癌的杀伤作用。结果MSLN在原发性卵巢癌组织和卵巢癌细胞系中高表达。流式细胞术检测显示靶向MSLN的CAR-NK-92纯度为70%左右。体内和体外实验发现靶向MSLN的CAR-NK-92细胞具有较强抗卵巢癌作用,能释放更多的细胞因子干扰素-γ和肿瘤坏死因子-α。结论靶向MSLN的CAR-NK-92具有较强的体内和体外抗卵巢癌作用,为卵巢癌患者提供了潜在治疗方案。

Objective To explore the killing effect of chimeric antigen receptoRNK-92(CAR-NK-92)cells targeting mesothelin(MSLN)on ovarian canceRcells.Methods The expression of MSLN in primary ovarian canceRtissues and ovarian canceRcell lines was detected by immunohistochemical analysis and immunofluorescence,respectively.The CAR-NK-92 cells targeting MSLN were constructed by lentiviral transfection,the transfection efficiency was detected by flow cytometry,and the killing effect of CAR-NK-92 on ovarian canceRwas verified in vivo and in vitro.Results MSLN was highly expressed in primary ovarian canceRtissues and ovarian canceRcell lines.Flow cytometry showed that the purity of CAR-NK-92 targeting MSLN was about 70%.The experiments found that MSLN-CAR-NK-92 cells had a strong anti-ovarian canceReffect in vivo and in vitro,and could release more cytokines interferon-γand tumoRnecrosis factor-α.Conclusion MSLN-CAR-NK-92 has strong anti-ovarian canceReffects in vivo and in vitro,providing a new potential treatment option foRovarian canceRpatients.