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Cancer Immunotherapy Using Engineere...

Gschweng, Eric Hans.

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Cancer Immunotherapy Using Engineered Hematopoietic Stem Cells.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Cancer Immunotherapy Using Engineered Hematopoietic Stem Cells./
Author:	Gschweng, Eric Hans.
Description:	162 p.
Notes:	Source: Dissertation Abstracts International, Volume: 76-08(E), Section: B.
Contained By:	Dissertation Abstracts International76-08B(E).
Subject:	Immunology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3687407
ISBN:	9781321649536

Cancer Immunotherapy Using Engineered Hematopoietic Stem Cells.
Gschweng, Eric Hans.

Cancer Immunotherapy Using Engineered Hematopoietic Stem Cells. - 162 p.

Source: Dissertation Abstracts International, Volume: 76-08(E), Section: B.

Thesis (Ph.D.)--University of California, Los Angeles, 2015.

This item is not available from ProQuest Dissertations & Theses.

Engineering the immune system against cancer ideally provides surgical precision against the antigen bearing target cell while avoiding the systemic, off-target toxicity of chemotherapy. Successful treatment of patients in the clinic has been achieved by the expression of anti-cancer T-cell receptors (TCR) and chimeric antigen receptors (CAR) in T cells followed by infusion of these cells into cancer patients. Unfortunately, while many patients initially respond showing anti-tumor efficacy, the effects are by and large transient with the majority of patients succumbing to disease. This observation speaks to the power of the engineered antigen receptor, but also indicates a need for a persistent source of cells to mount a continuous response.

ISBN: 9781321649536Subjects--Topical Terms:

611031
Immunology.

Cancer Immunotherapy Using Engineered Hematopoietic Stem Cells.
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100 1 $a Gschweng, Eric Hans. $3 3192913
245 1 0 $a Cancer Immunotherapy Using Engineered Hematopoietic Stem Cells.
300 $a 162 p.
500 $a Source: Dissertation Abstracts International, Volume: 76-08(E), Section: B.
500 $a Adviser: Donald B. Kohn.
502 $a Thesis (Ph.D.)--University of California, Los Angeles, 2015.
506 $a This item is not available from ProQuest Dissertations & Theses.
520 $a Engineering the immune system against cancer ideally provides surgical precision against the antigen bearing target cell while avoiding the systemic, off-target toxicity of chemotherapy. Successful treatment of patients in the clinic has been achieved by the expression of anti-cancer T-cell receptors (TCR) and chimeric antigen receptors (CAR) in T cells followed by infusion of these cells into cancer patients. Unfortunately, while many patients initially respond showing anti-tumor efficacy, the effects are by and large transient with the majority of patients succumbing to disease. This observation speaks to the power of the engineered antigen receptor, but also indicates a need for a persistent source of cells to mount a continuous response.
520 $a This thesis work sought to investigate the feasibility of engineering immunity using hematopoietic stem cells (HSC). HSC are at the top of the hematopoietic hierarchy, and would theoretically provide a continuous supply of antigen receptor bearing T cells capable of eliminating disease in a patient. Important considerations for using HSCs in gene therapy include: efficient gene delivery to HSCs which are refractory to gene modification by nature, robust expression of the transgene within gene modified cells to provide efficacy, evaluation of successful gene modification and engraftment following transplant, the ability of gene modified T cells to mount an immune response against their intended targets, and the ability to eliminate the gene modified cells in the event of undesired outcomes.
520 $a Current systems to study human HSC biology and gene therapy are limited, and the best available are human / mouse chimeric transplant systems. Using these models, we evaluated the utility of positron emission tomography (PET) in the humanized mouse following transplant of gene modified cells, and found it superior to peripheral blood flow cytometry in being able to temporally establish successful engraftment. Using a lentiviral vector expressing both a TCR against a common cancer / testes antigen, NY-ESO-1, as well as a PET imaging / suicide gene, we demonstrated the ability to monitor engraftment, successful generation of effector cells capable of killing patient derived cancer cell lines, and the complete elimination of gene modified cells. This final work provides support for a clinical trial soon to enroll patients at UCLA.
520 $a The use of HSCs for engineered cancer immunotherapy could overcome current limitations associated with the lack of persistence of engineered terminally differentiated immune cells. Further, the rich clinical history of gene therapy using HSCs provides a broad platform for future studies aimed at the broad spectrum of cancer disease.
590 $a School code: 0031.
650 4 $a Immunology. $3 611031
650 4 $a Pharmacology. $3 634543
690 $a 0982
690 $a 0419
710 2 $a University of California, Los Angeles. $b Microbiology, Immunology, and Molecular Genetics. $3 3183000
773 0 $t Dissertation Abstracts International $g 76-08B(E).
790 $a 0031
791 $a Ph.D.
792 $a 2015
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3687407