The development of next-generation antibody based therapeutics for the treatment of pancreatic cancer

Pancreatic cancer is an extremely challenging disease in dire need of improved detection methods and therapeutics. Currently, less than 20% of patients are eligible for surgery at the time of diagnosis, the only potentially curative treatment regimen available. Many of the remaining 80%+ of patients lack the physical fitness to tolerate the current first-line chemotherapeutic combination therapy FOLFIRINOX, due to the significant toxicities associated with treatment. This highlights the urgent need for researchers to identify novel therapeutic agents capable of providing tangible patient benefit in the clinic.<br/><br/>Increasingly, researchers have acknowledged that in pancreatic cancer, profound disease control is unlikely to be achieved utilising single agent treatment methodologies. Efforts should now focus on the identification and validation of rationale combinations, utilising synergistic mechanisms of action to exploit multiple disease vulnerabilities. Monoclonal antibodies and their derivatives are an avenue worth exploring for utilisation in combination therapeutic approaches. They have previously revolutionised the field of oncology and their potential has not yet been exhausted. A novel potential clinical application of antibodies is their incorporation into nanomedicine platforms as both targeting ligands and effector molecules, to facilitate both improved drug delivery and synergistic signalling for enhanced disease control via ‘active targeting’.<br/><br/>This thesis attempts to develop and validate novel antibody conjugated, nanoparticle-based delivery systems for cytotoxic payloads. Alongside this, novel antibodies targeted against a range of targets were also developed, for their incorporation into treatment strategies for pancreatic cancer.<br/><br/>In summary, this thesis describes the development of a range of antibody-based therapeutics, furthering current understandings of nanoparticle-based delivery systems and the therapeutic potential of next-generation antibody-based therapeutics for the treatment of pancreatic cancer.<br/><i><br/>Thesis embargoed until 31 July 2027</i>.

Name dc:type.qualificationname

Doctor of Philosophy

Level dc:type.qualificationlevel

Doctoral Thesis

Grantor dc:publisher.institution

Queen's University Belfast

Year dc:date.issued

2022

Author dc:creator

• Boland, Anna

Advisors dc:contributor.advisor

• Longley, Daniel
• Scott, Christopher

Language dc:language

eng

Identifier

oai:pure.qub.ac.uk/portal:studenttheses/46f760b6-d565-46c2-9001-93c47fd74099

OAI identifier oai:identifier

oai:pure.qub.ac.uk/portal:studenttheses/46f760b6-d565-46c2-9001-93c47fd74099