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Ian Miller
PhD Proposal Presentation
Date: March 12, 2019
Time: 10:00 am
Location: EBB Room 3029
Advisor:
Dr. Gabriel Kwong, PhD
Wallace H. Coulter Department of Biomedical Engineering
Georgia Institute of Technology and Emory University
Committee Members:
Dr. Koichi Araki
Department of Microbiology and Immunology
Emory University
Dr. Erik Dreaden
Wallace H. Coulter Department of Biomedical Engineering
Georgia Institute of Technology and Emory University
Dr. Krishnendu Roy
Wallace H. Coulter Department of Biomedical Engineering
Georgia Institute of Technology and Emory University
Dr. Susan Thomas
George W. Woodruff School of Mechanical Engineering
Georgia Institute of Technology
Title: "Remote Control of Adoptive T cell Therapies"
Abstract:
Recent advances in engineered T cell therapies are providing physicians with a rapidly expanding repertoire of cell-based treatments to fight cancers that are otherwise refractory to conventional treatments. For example, strategies harnessing T cells engineered with chimeric antigen receptors (CARs) have resulted in dramatic disease regression, and in some patients, completely curative responses. Yet despite such striking progress, our ability to precisely control the cytotoxic activity of adoptively transferred T cells in vivo remains limited – especially within solid tumors. In contrast to hematological malignancies, solid tumors have the uncanny ability to evade the immune system by creating an immunosuppressive microenvironment that inhibits effector cells’ ability to kill tumor cells. Furthermore, CARs target antigens expressed by both diseased and healthy tissues and the inability to tune CAR T cell activity has resulted in deleterious, off-tumor effects ranging from B cell aplasia to Cytokine Release Syndrome (CRS) and fatal off-target cytotoxicity. Ideally the next generation of engineered T cell therapies would include the capacity to be remotely controlled by external cues, such as light or heat, to enable localized control of immune responses including cytokine signaling, maintenance and proliferation of effector populations, and anti-tumor cytotoxicity. Achieving this degree of precision will increase the safety and potency of engineered T cell therapies for cancer. Inspired by thermal medicine, I will explore a framework for remote control of T cell therapies by heat. I propose engineering thermal gene switches to allow heat-triggered expression of potent immunostimulatory cytokines and expression of tumor-specific CARs; the therapeutic efficacy of this strategy will be evaluated in preclinical cancer models of adoptive cell therapies. I envision that the framework established by this proposal will provide clinicians new methods to treat unresponsive tumors and advance the field of precision medicine.
