Macrophages are a member of the innate arm of the human immune system and are central to both the initiation and perseverance of the immune response with the ability to provide signals of both an inflammatory and an anti-inflammatory nature. Dysfunction in either direction can lead to wide range of disorders. Owing to their role in immunity and inflammation, macrophages make an enticing target for the generation of a therapeutic.
Chimeric Antigen Receptors (CAR) have been applied to T cells to combat cancer and are more recently being tested in macrophages for similar utility. Currently, autologous cells are harvested from the patient and modified to carry the CAR which is a fusion of an extracellular targeting moiety to an intracellular activating domain that is itself a fusion of the cytoplasmic signaling arms needed to activate the T cells or macrophages. Use in this manner drives pro-inflammatory activation in order to kill tumor cells. The work in this thesis aims to repurpose the CAR to harness the anti-inflammatory side of macrophages in order clear inflammation in various disease states such as Rheumatoid Arthritis (RA) that have proven difficult to cure.
|Commitee:||Gorski, Stacey, McCabe, Timothy, Walasek, Carl|
|School:||University of the Sciences in Philadelphia|
|Department:||Cell & Molecular Biology|
|School Location:||United States -- Pennsylvania|
|Source:||DAI-B 81/10(E), Dissertation Abstracts International|
|Keywords:||Anti-inflammatory, Chimeric antigen receptor, Macrophage|
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