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MSCTRAIL Treatment of Thoracic Cancer

Davies, Alice; (2020) MSCTRAIL Treatment of Thoracic Cancer. Doctoral thesis (Ph.D), UCL (University College London).

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Lung cancer is the leading cause of cancer death worldwide with 5 year survival in the UK estimated at just 16%[1-3]. For patients with advanced non-small cell lung cancer treatment can offer some survival benefit but is often associated with poorly tolerated side effects. Mesenchymal stromal cells (MSCs) possess innate characteristics which make them suited for use as a therapy, including the ability to home to and incorporate into sites of cancer [4]. TNF related apoptosis inducing ligand (TRAIL) has been shown to cause selective cancer cell death, via the extrinsic death pathway [5]. It has been demonstrated that MSCs can be transduced with a lentiviral vector to express TRAIL and that MSCTRAIL will home to and induce apoptosis of tumour cells in vitro and reduce tumour growth in multiple in vivo models[6] however it has not been trialled as a clinical therapy before. In order to move from ‘bench to bedside’ a phase I/II trial was set up to establish the safety and efficacy of MSCTRAIL in combination with first line standard of care therapies for advanced adenocarcinoma of the lung- The TACTICAL trial. TACTICAL has recruited and treated four patients and successfully delivered nine doses of MSCTRAIL to those patients. At efficacy evaluation one patient had unconfirmed progressive disease, one has stable disease and two had partial response (by iRECIST criteria), no patients experienced dose limiting toxicities. The first three patients were incidentally found to have asymptomatic pulmonary embolisms. This led to a serious adverse event review, temporary pause to the trial and alterations to the protocol before it could re-open. Lung cancer is a devastating disease with high mortality rates and poor treatment options. Presented here is the initial clinical work carried out to investigate if MSCTRAIL is a safe and effective treatment for metastatic adenocarcinoma of the lung.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: MSCTRAIL Treatment of Thoracic Cancer
Event: UCL
Language: English
Additional information: Copyright © The Author 2020. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
Keywords: lung cancer, MSCs, Adenocarcinoma, Mesechymal Stromal Cells, MSCTRAIL, TRAIL
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10109127
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