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DEVELOPMENT AND IN VITRO ASSESSMENT OF A PRETARGETED DELIVERY SYSTEM FOR CANCER SITE SPECIFIC DELIVERY OF PROTEINS

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title
DEVELOPMENT AND IN VITRO ASSESSMENT OF A PRETARGETED DELIVERY SYSTEM FOR CANCER SITE SPECIFIC DELIVERY OF PROTEINS
author
Yeh, Stacy
abstract
Improved delivery of therapeutics to cancer cells is still an important topic in cancer research. While targeted delivery using antibody-drug conjugates has proven to be a valuable strategy, problems such as long circulation times and poor selectivity are still present. Pretargeting is a novel delivery strategy used for improving site specific delivery of therapeutics. In the pretargeting process, a targeting molecule consisting of an antibody and a linker binds to the surface target of cancers cells. Once the therapeutic molecule, which includes the complementary linker is given, conjugation occurs. Despite broad application in radioimmunoimaging and radioimmunotherapy, pretargeting for protein delivery is still relatively unexplored. In this work, different cancer targets were assessed for pretargeting, and a pretargeting method for protein delivery using click chemistry conjugation was developed for specificity to cancer cells. The proteins studied were TNF, a cytokine produced by immune cells with roles in cytotoxicity and inflammation, and kynureninase, an enzyme which metabolizes immunosuppressive kynurenine. In vitro studies show successfully delivery of proteins to the surface of cancer cells using our pretargeting approach. Further, both surface-anchored proteins maintained biological activity in vitro. Using this method, we have achieved site specific delivery of proteins using a pretargeted delivery strategy.
subject
Cancer
Drug Delivery
Pretargeting
contributor
Ming, Xin (committee chair)
Lee, Yong W (committee member)
Zhao, Dawen (committee member)
date
2021-09-01T08:35:36Z (accessioned)
2021 (issued)
degree
Biomedical Engineering (discipline)
embargo
2026-09-07 (terms)
2026-09-07 (liftdate)
identifier
http://hdl.handle.net/10339/99072 (uri)
language
en (iso)
publisher
Wake Forest University
type
Thesis

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