105197Investigating the therapeutic potential of biomarker targeted MSCTRAIL in malignant pleural mesotheliomaClosedCollaborative R&DInnovate UK"Malignant pleural mesothelioma (MPM) is a cancer affecting the lining of the lungs. It is usually caused by asbestos exposure and the number of cases is increasing with more than 2,500 cases per year in the UK. Mesothelioma is very difficult to treat and is incurable; the average life expectancy from diagnosis is 12-18 months. We have developed a new, genetically modified cell therapy that is able to find and kill cancer cells without affecting healthy cells. Our laboratory data shows that this cell therapy, a mesenchymal stromal cell (MSC) and gene therapy (called TRAIL) kills most malignant mesothelioma cells and is more effective than the chemotherapy drugs we currently use in patients. Used together they are extremely potent. In addition we have identified which patients' cancers the therapy is most likely to be effective against, using a biomarker (loss of a protein in cells called BAP1). The aim of this research project is to test whether this novel cell and gene therapy is effective in treating patients with MPM, more than half of whom carry that biomarker. We and other teams have shown MSCs are attracted to sites of cancer. We have modified these MSCs to express a protein called TRAIL that kills cancer cells but not normal cells. This means the MSCs can deliver TRAIL directly to the tumours and work at the site of the cancer. We have shown that these TRAIL-carrying MSCs kill a high percentage of mesothelioma cells from different patients and in particular those cells that don't express the protein BAP1\. When MSCTRAIL is given to mice with mesothelioma the growth of the tumours is significantly reduced. In order to test whether this treatment works, we will run a clinical trial in patients who have been diagnosed with MPM whose tumours do not express the BAP1 protein and are due to have the current recommended chemotherapy treatment. Patients will be allocated randomly to receive either the standard chemotherapy alone or the same chemotherapy but in combination with MSCTRAIL. Each patient will receive three doses of MSCTRAIL delivered by injection into a vein. Each dose will be given 3 weeks apart and at the end of 12 weeks they will have a scan of their chest to assess whether the mesothelioma has reduced in size."