利用白细胞介素武装病毒或可有效治疗胰腺癌

  近日，刊登在国际杂志Clinical Cancer Research上的一篇研究论文中，来自伦敦大学玛丽皇后学院的研究人员将两种不同的方法：病毒疗法和免疫疗法相结合开发出了一种治疗胰腺癌的潜在疗法。

  文章中，研究人员调查了牛痘溶瘤细胞病毒治疗胰腺癌的效果，牛痘溶瘤细胞病毒是一种修饰后可以选择性感染并杀灭癌细胞的病毒；当给予该病毒装备上可以调节机体免疫系统的基因后就可以更有效地杀灭胰腺癌细胞；尽管实验室研究显示这种联合作用可以杀灭癌细胞并且抵御癌症细胞的生长，但溶瘤病毒在临床试验中表现并不理想，在其发挥作用前机体免疫系统往往会攻击病毒。

  本文研究中，研究人员利用白细胞介素-10（IL-10）基因来“武装” 牛痘溶瘤病毒，这样其就可以在癌细胞中表达特殊的蛋白质，这种蛋白质对于细胞信号非常重要，但却可以减弱机体免疫反应，研究者Yaohe Wang说道，许多病毒都可以利用IL-10来隐藏，因此我们就可以利用这种天然的策略来调查是否其可以改善牛痘溶瘤病毒的作用效力。

  首先研究者在细胞系研究中证实了，以IL-10装备病毒后并不会中和病毒的抗癌作用，随后研究者对患胰腺癌的小鼠进行试验，6周实验后，利用联合疗法（武装IL-10的牛痘溶瘤病毒）处理的小鼠中有87.5%的个体机体中的肿瘤都被完全清除了，而仅用牛痘溶瘤病毒治疗的小鼠中却又42.8%的个体肿瘤被清除，使用联合疗法后转基因小鼠的平均生存期由原来的69.7天增加到了138.5天。

  最后研究者表示，我们的研究揭示在小鼠机体中IL-10可以抑制抗病毒免疫力，但是会增强抗肿瘤免疫力，后期我们还需要更多的研究来以IL-10装备的病毒来设计出更加有效地治疗胰腺癌的策略。（转化医学网360zhyx.com）

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转化医学网推荐的原文摘要：

A Vaccinia virus armed with interleukin-10 is a promising therapeutic agent for treatment of murine pancreatic cancer.
Clinical Cancer Research DOI: 10.1158/1078-0432.CCR-14-0464
Louisa Chard1, Eleni Maniati2, Pengju Wang3, Zhongxian Zhang3, Dongling Gao3, Jiwei Wang3, Fengyu Cao4, Jahangir Ahmed1, Margueritte EI Khouri1, Jonathan Hughes1, Shengdian Wang5, Xiaozhu Li6, Bela Denes7, Istvan Fodor8, Thorsten Hagemann9, Nicholas R. Lemoine10, and Yaohe Wang1,*
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 (VVL∆TK-IL10) and control VV∆TK 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 VVL∆TK, VVL∆TK-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 VVL∆TK-IL10 was reduced at early time points compared to the control virus. Treatment with VVL∆TK-IL10 resulted in a reduction in virus-specific, but not tumor-specific CD8+ cells compared to VVL∆TK. Conclusions:These results suggest that VVL∆TK-IL10 has strong potential as an antitumor therapeutic for PaCa.