Loebinger, M.R.; (2009) Mesenchymal stem cells as vectors for anti-tumour therapy. Doctoral thesis , UCL (University College London).

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Abstract

Cancer is a leading cause of mortality throughout the world and new treatments are urgently needed. Recent studies suggest that bone marrow-derived mesenchymal stem cells (MSCs) home to and incorporate within tumour tissue. This property can be utilised to deliver targeted anticancer therapies. This thesis describes the production of MSCs engineered to express TNF-related apoptosis-inducing ligand (TRAIL), a transmembrane protein that causes selective apoptosis of tumour cells. Human MSCs were transduced with TRAIL and the IRES-GFP reporter gene using a lentiviral vector, under the control of a tetracycline promoter. Transduced and activated MSCs caused lung, breast, squamous, and cervical cancer cell apoptosis in vitro. In vivo, the cells were able to specifically home to tumours and both significantly reduce tumour growth, and eliminate metastatic disease. The data included in this thesis demonstrates for the first time a significant reduction in metastatic tumour burden with frequent eradication of metastases using inducible TRAIL-expressing MSCs. This has a wide potential therapeutic role, which includes the treatment of both primary tumours and their metastases, possibly as an adjuvant therapy in clearing micrometastatic disease following primary tumour resection.

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