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Synthetic Biology Approaches to Impr...
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Cho, Jang Hwan.
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Synthetic Biology Approaches to Improve Cell-Based Cancer Immunotherapy.
紀錄類型:
書目-電子資源 : Monograph/item
正題名/作者:
Synthetic Biology Approaches to Improve Cell-Based Cancer Immunotherapy./
作者:
Cho, Jang Hwan.
出版者:
Ann Arbor : ProQuest Dissertations & Theses, : 2019,
面頁冊數:
184 p.
附註:
Source: Dissertations Abstracts International, Volume: 81-03, Section: B.
Contained By:
Dissertations Abstracts International81-03B.
標題:
Biomedical engineering. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13857335
ISBN:
9781085619134
Synthetic Biology Approaches to Improve Cell-Based Cancer Immunotherapy.
Cho, Jang Hwan.
Synthetic Biology Approaches to Improve Cell-Based Cancer Immunotherapy.
- Ann Arbor : ProQuest Dissertations & Theses, 2019 - 184 p.
Source: Dissertations Abstracts International, Volume: 81-03, Section: B.
Thesis (Ph.D.)--Boston University, 2019.
This item must not be sold to any third party vendors.
Adoptive 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.
ISBN: 9781085619134Subjects--Topical Terms:
535387
Biomedical engineering.
Subjects--Index Terms:
Anti-cancer therapy
Synthetic Biology Approaches to Improve Cell-Based Cancer Immunotherapy.
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Adoptive 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.
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