干细胞基因疗法治疗肺癌进入临床阶段

  近日，来自伦敦大学的研究人员计划开展一项新的研究，即利用干细胞基因疗法治疗肺癌患者，这项对56名患者进行的临床试验是英国首次利用干细胞基因结合疗法来治疗癌症患者的新型试验。

  研究者Sam Janes表示，这项研究将由我来领导，而且这项研究是基于我们之前的工作来开展的，此前研究中研究者揭示了工程化的间充质干细胞可以过量表达肿瘤坏死因子相关细胞凋亡诱导配体(tumor necrosis factor-related apoptosis-inducing ligand，TRAIL)，TRAIL是TNF超家族的新成员，可以诱导多种肿瘤细胞凋亡，但对大多数正常细胞无影响。

  研究者发现，当对间皮瘤小鼠进行治疗后，这种干细胞基因疗法可以增加肿瘤的负担，抑制其生长，并且可以增加由TRAIL诱导的细胞凋亡过程。如今研究者已经获得来自英国医学研究理事会(MRC)自主的300万美元来研究是否将干细胞基因疗法同化疗相结合可以为患者带来比标准化疗法更多的益处。

  在临床试验中，研究者将会为56个肺癌患者中的每一个注入近乎10亿个工程化的TRAIL表达的干细胞来进行疾病的治疗；试验中每个患者均进行三次注射，中间间隔3周，注射完一天后随即进行化疗方法治疗。为了评估并且比较化疗和干细胞基因疗法组合疗法同单一标准疗法之间的产别，研究者认为，如果试验结果良好，那么或许将为开发治疗肺癌患者的新型疗法带来巨大帮助。

  值得注意的是，干细胞并不需要来自于亲属或者自身机体匹配的组织，因为其表达蛋白的相对缺失会使得机体不会产生免疫反应；置于干细胞内部物质会被保护起来不被降解，理论上来讲可以使得TRAIL蛋白到达靶向受体上并且诱发肿瘤细胞凋亡。其它运输TRAIL的方法都不是很理想，因为TRAIL蛋白在达到靶点前都会被变性。

  最后研究者说道，如果干细胞运输工具可以提供一种防御机制，其或许可以促进TRAIL来诱发一系列癌细胞的凋亡，但是后期还需要进行大量临床试验才可以进行验证。（转化医学网360zhyx.com）

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A team of London-based academics is set to study a stem cell-delivered gene therapy in patients with lung cancer. The 56-person trial is the first time a stem cell-gene therapy combination has been tested in humans in the U.K.

University College London's Professor Sam Janes will lead the study, which builds on preclinical work he and his collaborators published late last year. The paper showed the potential of engineering mesenchymal stromal cells to overexpress tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). When administered to mice with mesothelioma, the stem cell-gene therapy combo was associated with a drop in tumor burden and an uptick in the apoptosis process that is triggered by the TRAIL protein.

Now, the researchers have snagged £2 million ($3 million) from the Medical Research Council (MRC) to investigate whether combining the treatment with chemotherapy results in better outcomes than the standard of care. The clinical trial will give almost one billion of the engineered, TRAIL-expressing stem cells to each of the 56 lung cancer patients that participate. Each patient will receive three infusions, three weeks apart and one day after they are treated with chemotherapy.

The objective is to assess how the treatment compares to standard of care. If the data are favorable, they could lead to the treatment advancing into larger lung cancer trials and the therapeutic approach being applied to other indications. Several features of the treatment make it attractive for such an expansion. Notably, the stem cells don't need to come from a relative or tissue match because the comparative lack of proteins on their surface means the body doesn't mount an immune response.

Material inside the cell is protected from degradation, theoretically allowing the TRAIL protein to reach target receptors and trigger apoptosis. Other attempts to deliver TRAIL have faltered because the protein was denatured before it reached its target. If the stem cell delivery vehicle provides a way around these defenses, it could enable TRAIL to trigger apoptosis in a range of cancers. For now, that "if" remains a sizable unknown. "This is truly experimental," Janes told The Guardian.....