Engineering VHH-based chimeric antigen receptor (CAR) T cell therapy for solid tumor treatment
Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biological Engineering, 2019
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| Format: | Thesis |
| Language: | eng |
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Massachusetts Institute of Technology
2019
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| Online Access: | https://hdl.handle.net/1721.1/123070 |
| _version_ | 1811094303859015680 |
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| author | Xie, Yushu Joy. |
| author2 | Hidde L. Ploegh. |
| author_facet | Hidde L. Ploegh. Xie, Yushu Joy. |
| author_sort | Xie, Yushu Joy. |
| collection | MIT |
| description | Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biological Engineering, 2019 |
| first_indexed | 2024-09-23T15:57:54Z |
| format | Thesis |
| id | mit-1721.1/123070 |
| institution | Massachusetts Institute of Technology |
| language | eng |
| last_indexed | 2024-09-23T15:57:54Z |
| publishDate | 2019 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/1230702019-11-22T03:03:41Z Engineering VHH-based chimeric antigen receptor (CAR) T cell therapy for solid tumor treatment Engineering Volatile Halogenated Hydrocarbons-based chimeric antigen receptor (CAR) T cell therapy for solid tumor treatment Xie, Yushu Joy. Hidde L. Ploegh. Massachusetts Institute of Technology. Department of Biological Engineering. Massachusetts Institute of Technology. Department of Biological Engineering Biological Engineering. Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biological Engineering, 2019 Cataloged from PDF version of thesis. Includes bibliographical references. Chimeric antigen receptor (CAR) T cells are a promising cancer therapeutic, as they can specifically redirect the cytotoxic function of a T cell to a chosen target of interest. CAR T cells have been successful in clinical trials against hematological cancers, but have experienced low efficacy against solid tumors for a number of reasons, including a paucity of tumor-specific antigens to target and a highly immunosuppressive solid tumor microenvironment. In chapter 2 of this thesis, we develop a strategy to target multiple solid tumor types through markers in their microenvironment. The use of single domain antibody (VHH)-based CAR T cells that recognize these markers circumvents the need for tumor-specific targets. Chapter 3 will describe methods to overcome the immunosuppressive microenvironment of solid tumors. Here, we have developed VHH-secreting CAR T cells that can modulate additional aspects of the tumor microenvironment, including the engagement of the innate immune system through secretion of a VHH against an inhibitor of phagocytosis. We show that this strategy of VHH-secretion by CAR T cells can lead to significant benefits in outcome. We also demonstrate that delivery of therapeutics by CAR T cells can improve the safety profile of the therapeutic. Chapter 4 of this thesis explores strategies to increase the targeting capacity of CAR T cells by building logic-gated CARs. Finally, chapter 5 will describe work in imaging CAR T cells specifically, longitudinally, and non-invasively through PET imaging. Our results demonstrate the flexibility of VHHs in CAR T cell engineering and the potential of VHH-based CAR T cells to target the tumor microenvironment, modulate the tumor microenvironment, and treat solid tumors. by Yushu Joy Xie. Ph. D. Ph.D. Massachusetts Institute of Technology, Department of Biological Engineering 2019-11-22T00:09:44Z 2019-11-22T00:09:44Z 2019 2019 Thesis https://hdl.handle.net/1721.1/123070 1127385442 eng MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission. http://dspace.mit.edu/handle/1721.1/7582 154 pages application/pdf Massachusetts Institute of Technology |
| spellingShingle | Biological Engineering. Xie, Yushu Joy. Engineering VHH-based chimeric antigen receptor (CAR) T cell therapy for solid tumor treatment |
| title | Engineering VHH-based chimeric antigen receptor (CAR) T cell therapy for solid tumor treatment |
| title_full | Engineering VHH-based chimeric antigen receptor (CAR) T cell therapy for solid tumor treatment |
| title_fullStr | Engineering VHH-based chimeric antigen receptor (CAR) T cell therapy for solid tumor treatment |
| title_full_unstemmed | Engineering VHH-based chimeric antigen receptor (CAR) T cell therapy for solid tumor treatment |
| title_short | Engineering VHH-based chimeric antigen receptor (CAR) T cell therapy for solid tumor treatment |
| title_sort | engineering vhh based chimeric antigen receptor car t cell therapy for solid tumor treatment |
| topic | Biological Engineering. |
| url | https://hdl.handle.net/1721.1/123070 |
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