Int J Mol Sci:在膀胱癌中,以CD46为靶标能够增加腺病毒5型的抗肿瘤活性

2018-10-02 AlexYang MedSci原创

CD46在许多人类癌症中是过表达的,也是CD46结合腺病毒(Ads)的一个主要的靶标。这能够帮助人们克服柯萨奇腺病毒受体(CAR)为靶标的癌症基因治疗病毒抗肿瘤活性的降低。然而,由于缺乏CAR和CD46在各种癌症中表达水平的信息,研究人员对癌症治疗效果进行了混合观察。研究人员评估了Ad介导并且使用CAR靶向Ad5或者CD46靶向Ad5/35纤维嵌合体在膀胱癌细胞系中的治疗效果。与正常上皮比较,膀胱

CD46在许多人类癌症中是过表达的,也是CD46结合腺病毒(Ads)的一个主要的靶标。这能够帮助人们克服柯萨奇腺病毒受体(CAR)为靶标的癌症基因治疗病毒抗肿瘤活性的降低。然而,由于缺乏CAR和CD46在各种癌症中表达水平的信息,研究人员对癌症治疗效果进行了混合观察。

研究人员评估了Ad介导并且使用CAR靶向Ad5或者CD46靶向Ad5/35纤维嵌合体在膀胱癌细胞系中的治疗效果。与正常上皮比较,膀胱癌组织基本上均过表达CAR和CD46.虽然CAR表达与疾病的恶化没有联系,CD46的表达与肿瘤等级、阶段和风险等级争先负相关关系。在膀胱癌细胞系中,CD46和CAR的表达水平与Ad5/35和Ad5介导的基因转化和细胞毒性分别高度相关。在一个人类EJ膀胱癌异种种植小鼠模型中,伴随着CD46基因的过表达或者抑制表达,Ad5/35-tk之后更昔洛韦(GCV)治疗能够显著的影响肿瘤生长,而 Ad5-tk/GCV单独使用时影响很小。

最后,研究人员指出,他们的研究表明了膀胱癌细胞过表达CAR和CD46,以CD46为靶标的腺病毒癌症基因治疗代表了一种比以CAR为靶标治疗更加合适的治疗选择,尤其是在那些低风险膀胱癌患者中。

原始出处:

Do MH, To PK, Cho YS et al. Targeting CD46 Enhances Anti-Tumoral Activity of Adenovirus Type 5 for Bladder Cancer. Int J Mol Sci. 10 Sep 2018.

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    2019-02-11 qidongfanjian
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    2018-10-04 zhaojie88

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