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首页 » 癌症研究 » Clin Cancer Res:IL-10基因装备病毒有望更好治疗胰腺癌

Clin Cancer Res:IL-10基因装备病毒有望更好治疗胰腺癌

来源:生物谷 2014-12-26 14:46

2014年12月26日讯 /生物谷BIOON/ --两种不同的方法的组合,即病毒治疗及免疫治疗组合显示出治疗胰腺癌的“巨大潜力”。

一项由英国慈善胰腺癌症研究基金会资助的研究调查是否溶瘤牛痘病毒(经修饰以选择性地感染和杀死癌细胞的病毒)通过装备能调节机体免疫系统的一个基因后,能否更有效治疗胰腺癌。

虽然实验研究表明组合后既可以杀死癌细胞,也可以提振针对癌症再生的免疫力。但溶瘤病毒在临床试验并没有表现良好的治疗功效,因为免疫系统在他可以发挥有效前会攻击病毒。

研究团队用白介素-10(IL-10)基因的拷贝装备溶瘤牛痘病毒,一旦癌细胞感染牛痘病毒后,牛痘病毒会表达IL-10。这一蛋白质已知可以抑制免疫应答,研究者希望这会让病毒在体内持续更长时间。

很多病毒利用IL-10逃避宿主的免疫系统,所以我们调查这种组合策略是否提高病毒的有效性。该研究小组在细胞系中发现,牛痘病毒装备IL-10后,不会影响牛痘病毒的抗癌作用。然后,他们将牛痘病毒单独使用,牛痘病毒与IL-10组合比较,比较两组对小鼠胰腺癌以及一组转基因小鼠(以使其发生胰腺癌)的治疗有效性。六周后,用相结合方法治疗的小鼠中有87.5%小鼠体内肿瘤被完全清除,42.8%的牛痘病毒单独处理小鼠体内肿瘤被完全清除。研究人员说:这些都是令人振奋的结果,但我们仍然有几个问题,在小鼠中IL-10如何抑制抗病毒免疫,增强抗肿瘤免疫的,究竟IL-10如何使这种情况发生的仍不清楚。(生物谷Bioon.com)

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A Vaccinia virus armed with interleukin-10 is a promising therapeutic agent for treatment of murine pancreatic cancer

Louisa Chard, et al.

Purpose:Vaccinia virus (VV) has strong potential as a novel therapeutic agent for treatment of pancreatic cancer (PaCa). We investigated whether arming VV with IL10 could enhance the antitumor efficacy with the view that IL10 might dampen the host immunity to the virus, increasing viral persistence thus maximising the oncolytic effect and antitumor immunity associated with VV. Experimental Design:The antitumor efficacy of IL10-armed VV (VVLTK-IL10) and control VVTK was assessed in pancreatic cancer cell lines, mice bearing subcutaneous PaCa tumors and a PaCa transgenic mouse model. Viral persistence within the tumors was examined and immune depletion experiments as well as immunophenotyping of splenocytes were carried out to dissect the functional mechanisms associated with the viral efficacy. Results:Compared to unarmed VVLTK, VVLTK-IL10 had a similar level of cytotoxicity and replication in vitro in murine pancreatic cancer cell lines, but rendered a superior anti-tumor efficacy in the subcutaneous pancreatic cancer model and a K-ras-p53 mutant-transgenic PaCa model after systemic delivery, with induction of long-term antitumor immunity. The antitumor efficacy of the VV was dependent on CD4+ and CD8+, but not NK cells. Clearance of VVLTK-IL10 was reduced at early time points compared to the control virus. Treatment with VVLTK-IL10 resulted in a reduction in virus-specific, but not tumor-specific CD8+ cells compared to VVLTK. Conclusions:These results suggest that VVLTK-IL10 has strong potential as an antitumor therapeutic for PaCa.

 

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