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dc.contributor.advisorWong, Wilson W.en_US
dc.contributor.advisorCollins, James J.en_US
dc.contributor.authorCho, Jang Hwanen_US
dc.date.accessioned2019-06-28T17:08:59Z
dc.date.available2019-06-28T17:08:59Z
dc.date.issued2019
dc.identifier.urihttps://hdl.handle.net/2144/36144
dc.description.abstractAdoptive T cell immunotherapy is a promising anti-cancer therapy that has the potential to become the ultimate therapeutic agents to treat a variety of diseases. Recently, chimeric antigen receptor (CAR) expressing T cells has demonstrated to be a very effective approach to treat B cell cancer patients. Despite optimistic results, there are several improvements that need to be made to enhance the safety and efficacy of current CAR T cell therapy. Fortunately, different synthetic biology tools can be implemented to overcome many of the current deficiencies of CAR T cell therapy. Here, we develop anti-Axl CAR and synNotch receptors to target Axl which is a tyrosine kinase receptor that is commonly overexpressed in many cancers and considered as one of important cancer therapeutic targets. Next, we develop a split, universal, and programmable (SUPRA) CAR system that can be used to switch targets without re-engineering T cells, fine-tune T cell activation level, and sense and logically respond to multiple antigens. These multiple features are useful in mitigating tumor relapse, limiting CAR-T induced toxicities, and enhancing tumor specificity. Orthogonal SUPRA CARs are also used to control different cell types and signaling domains, enabling diverse immune responses from SUPRA CAR T cells. Lastly, we demonstrate that SUPRA CAR can redirect the activity of both innate and adaptive immune cell types. We also expand the logic capabilities of SUPRA CAR T cells by integrating three inputs in a single immune cell. We also show intercellular logic gate by engineering immune cell-cell interaction. We further demonstrate controlling endogenous immune cell polarization using SUPRA CAR T cells. These wide-ranges of SUPRA CAR applications imply its versatility as a platform for engineering cell-cell interactions with advanced logic functions to enhance efficacy and safety of cell-based cancer immunotherapy.en_US
dc.language.isoen_US
dc.subjectBiomedical engineeringen_US
dc.titleSynthetic biology approaches to improve cell-based cancer immunotherapyen_US
dc.typeThesis/Dissertationen_US
dc.date.updated2019-06-04T19:05:42Z
etd.degree.nameDoctor of Philosophyen_US
etd.degree.leveldoctoralen_US
etd.degree.disciplineBiomedical Engineeringen_US
etd.degree.grantorBoston Universityen_US


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