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