MSCTRAIL for lung cancer

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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.