Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Master of Science

Program

Medical Biophysics

Collaborative Specialization

Molecular Imaging

Supervisor

Ronald, John A.

2nd Supervisor

Foster, Paula J.

Co-Supervisor

Abstract

Chimeric antigen receptor (CAR) T cell therapy is an emerging cancer treatment that has shown remarkable success in the treatment of B cell malignancies. However, this therapy still has the potential to cause severe toxicities or poor treatment responses in some patients. An imaging tool for tracking CAR-T cells could provide important patient-specific data on CAR-T cell fate. In chapter 2, fluorine-19 magnetic resonance imaging (19F MRI) was evaluated as a method to track the location of 19F perfluorocarbon (PFC) labeled CAR-T cells non-invasively in a mouse model of B cell leukemia. We show for the first time that PFC labeled CAR-T cells can be detected with a 3 Tesla clinical MR scanner and that PFC labeled CAR-T cells show no significant difference in treatment response compared to unlabeled CAR-T cells as evaluated with bioluminescence imaging. Chapter 3 summarizes the study and discusses the limitations and future work.

Summary for Lay Audience

Chimeric antigen receptor T (CAR-T) cell therapy involves taking immune cells from a patient’s blood, reprogramming them to bind and kill cancer cells, and then injecting them back into the patient. This treatment has shown a lot of success in patients battling blood cancers such as leukemia, but current therapies still face problems such as harmful side effects and ineffective treatment of solid tumours. My project is to implement imaging techniques to track the fate of CAR-T cells after they have been injected into the body. Our technique will use fluorine-19 magnetic resonance imaging to allow us to see the location of the cells over time. Our methods will be useful for learning more about the negative treatment responses to CAR-T cell therapy and for building and assessing new CAR-T cell therapies that are safer and more effective against cancer. Importantly, this CAR-T cell tracking method should be highly translatable for use in patients receiving CAR-T cell therapies. This may eventually allow doctors to determine if the therapy will be effective at earlier time points so that they can continue or change the treatment plan, to better determine if a patient will have harmful side effects, as well as to better understand why the treatment might fail or succeed in certain patients.

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