Expanding the use of electroporation from cutaneous to intraluminal and systemic applications

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dc.contributor.advisor Soden, Declan en
dc.contributor.advisor Forde, Patrick en
dc.contributor.author Sadadcharam, Mira
dc.date.accessioned 2017-01-20T10:07:09Z
dc.date.available 2017-01-20T10:07:09Z
dc.date.issued 2015
dc.date.submitted 2015
dc.identifier.citation Sadadcharam, M. 2015. Expanding the use of electroporation from cutaneous to intraluminal and systemic applications. PhD Thesis, University College Cork. en
dc.identifier.endpage 183 en
dc.identifier.uri http://hdl.handle.net/10468/3484
dc.description.abstract Cancer is a global phenomenon transcending the boundaries of age, race, geography and socioeconomic background. As our understanding of cancer cell biology has improved, we have developed a growing appreciation of cancer as a systemic disease. However, our improved understanding has been matched by cancer cell evolution and it is becoming increasingly clear that the future of anti-cancer therapies lies in a multi-modal approach. In this thesis, we adopted a “three-legged stool” approach to anti-cancer therapy. The first leg encompasses primary tumour ablation. We developed the EndoVe device, enabling endoscopic electroporation of gastrointestinal tissues and tumours. We conducted a pre-clinical evaluation of the EndoVe prior to a phase I/II clinical study and validated the efficacy of the system in the treatment of cutaneous murine gastrointestinal tumours. In addition, we established the safety and utility of endoscopically-delivered electroporation through evaluation in a porcine model and by treating canine colorectal tumours. The second leg of our stool involved immunotherapy. We opted for a combination regime of Treg depletion and immunotherapy with the cytokine, pGMCSF-B7.1. While we observed a modest but significant improvement of primary tumour burden, the combination regime had the remarkable effect of eradicating pre-existing, established lung metastases when compared to the use of either treatment alone. The potential clinical implications of this should not be understated as nine out of ten cancer deaths are directly attributable to metastatic disease burden. The third and final leg of our anti-cancer strategy involved the development of a DNA-based enhanced expression vector (pEEV), with improved expression capabilities across a range of tissue histologies over standard non-viral DNA vectors. Following on from this observation, we then utilised this pEEV vector system in combination with the immune cytokine GMCSF-B7.1 leading to robust recruitment of immune effector cells with consequent potent, durable and transferable tumour antigen-specific responses. en
dc.format.mimetype application/pdf en
dc.language English en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2015, Mira Sadadcharam. en
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/3.0/ en
dc.subject Electroporation en
dc.subject Electrochemotherapy en
dc.subject EndoVe en
dc.subject Cancer immunogene therapy en
dc.subject Immune therapy en
dc.subject Gene therapy en
dc.title Expanding the use of electroporation from cutaneous to intraluminal and systemic applications en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral en
dc.type.qualificationname PhD (Medicine and Health) en
dc.internal.availability Full text available en
dc.check.info No embargo required en
dc.description.version Accepted Version
dc.description.status Not peer reviewed en
dc.internal.school Medicine en
dc.check.type No Embargo Required
dc.check.reason No embargo required en
dc.check.opt-out Not applicable en
dc.thesis.opt-out false
dc.check.embargoformat Not applicable en
ucc.workflow.supervisor d.soden@ucc.ie
dc.internal.conferring Autumn 2015 en

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© 2015, Mira Sadadcharam. Except where otherwise noted, this item's license is described as © 2015, Mira Sadadcharam.
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