MSCTRAIL for lung cancer

在世界范围内，癌症仍然是导致死亡和发病的主要原因之一。主要的癌症治疗包括手术、化疗和放疗；然而，尽管这些治疗方法有所改进，但许多肿瘤没有反应。重要的是，一旦癌症扩散到不止一个部位（转移），除了极少数情况外，大多数情况下都是无法治愈的。在常见的癌症中，肺癌是一个特别需要治疗的问题。仅在英国就有34000人死于肺癌，是男性和女性最大的癌症杀手。在85%的病例中，肺癌患者向医生报告的疾病已经扩散。这些患者的平均生存期为8个月。目前用于治疗已经扩散的肺癌的疗法包括化疗，这是一种通过静脉进行的治疗。化疗不以任何方式针对癌症，因此治疗的是整个身体，而不仅仅是癌症，这导致了治疗的广泛毒性。令人失望的是，只有大约40%的患者对这些疗法有反应，而且即使是那些幸运的人，他们的预期寿命也只提高了几个月。最近的一些发现导致了针对肿瘤基因缺陷的研究。不幸的是，这些缺陷只发生在不到10%的肺癌（腺癌）亚组中，甚至这些患者在大约9个月后对治疗停止反应。癌症治疗的诸多挑战之一是如何将抗癌治疗药物输送到癌症部位。我们和其他人最近已经证明，骨髓来源的干细胞（BMSCs）在被输送到静脉后能够特异性地迁移到肿瘤中并融入肿瘤中，这种特性可用于提供“靶向”抗癌治疗。利用这些细胞递送各种抗癌分子，静脉内递送的MSCs已被证明优先在乳腺癌、肺癌和黑色素瘤、卡波西氏肉瘤（KS）、结直肠癌和胶质瘤的癌症组织中移动并存活。在这项研究中，一种新的治疗转移性肺癌的方法将通过给予一种新的治疗方法（称为MSCTRAIL），它由携带抗癌基因（TRAIL）的细胞（MSCs）组成，在肺癌患者化疗后的第二天注射到他们体内。研究的第一部分将是I期临床试验，旨在找到对肺癌患者有益的最安全剂量。研究的第二部分将是II期临床试验，该试验将比较MSCTRAIL与化疗联合使用与单独化疗的效果。我们将通过测量肿瘤缩小了多少以及患者是否活得更长来做到这一点。如果成功，这种新的细胞和基因疗法将在更大的（III期）临床试验中进行测试。

Worldwide, cancer remains one of the leading causes of mortality and morbidity. The mainstay of cancer therapy includes treatment with surgery, chemotherapy and radiotherapy; however, despite improvements in these treatments, many tumours do not respond. Importantly, once a cancer has spread to more than one site (metastasised) it is, in all but the rarest cases, incurable. Of the common cancers lung cancers are a particular problem to treat. Lung cancer accounts for 34,000 deaths in the UK alone and is the biggest cancer killer of both men and women. In 85% of cases, patients with lung cancer present to their doctor with disease that has already spread. These patients have an average survival of 8 months. Current therapies used to treat lung cancers that have spread include chemotherapy, a treatment delivered into a vein. Chemotherapy is not targeted to the cancer in any way and therefore treats the whole body, not just the cancer, resulting in widespread toxicity from the treatment. Disappointingly only around 40% of patients will show any sign of their cancer responding to these therapies, and life expectancy, even in the lucky ones, is improved by a handful of months only. More recent discoveries have led to targeting of genetic defects in tumours. These defects unfortunately occur in less than 10% of a single subgroup of lung cancers (adenocarcinomas) and even these patients stop responding to treatment after around 9 months.One of the many challenges of cancer treatment relates to the delivery of the anti-cancer therapy to the cancer site. We, and others, have recently shown that bone marrow-derived stem cells (BMSCs) are able to migrate specifically to and incorporate within tumours after being delivered into a vein, and this property can be used to deliver 'targeted' anticancer therapies. Using these cells to deliver various anti-cancer molecules, intravenously delivered MSCs have been shown preferentially to move towards and survive in cancer tissue in breast, lung, and melanoma lung metastases, Kaposi's sarcoma (KS), colorectal cancer and gliomas.In this research, a novel treatment for metastatic lung cancer will be investigated by giving a new treatment (called MSCTRAIL), which consists of cells (MSCs) carrying an anti-cancer gene (TRAIL), injected into lung cancer patients a day after they have chemotherapy. The first part of the research will be a phase I clinical trial aiming to find the safest dose which will benefit a lung cancer patient. The second part of the research will be a phase II clinical trial which will compare what effect MSCTRAIL has when given with chemotherapy compared to chemotherapy alone. We will do this by measuring how much the tumour has become smaller and also whether patients live longer. If successful, this novel cell and gene therapy treatment will then be tested in a larger (phase III) clinical trial.