Ultrasound Control and Imaging of Cellular Immunotherapy

Citation

Lee, Justin (2024) Ultrasound Control and Imaging of Cellular Immunotherapy. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/60sh-a389. https://resolver.caltech.edu/CaltechTHESIS:03132024-155539035

Abstract

Biomedical ultrasound-based therapeutics and diagnostics are becoming an increasingly important clinical tool. Techniques like focused ultrasound tissue heating and microbubble-enhanced ultrasound imaging have enabled new ways to noninvasively treat and detect diseases cost-effectively and safely. While these are great leaps forward in ultrasound technology, leveraging synthetic biology tools to engineer cells with the capabilities to interact with ultrasound in novel ways may enable even more avenues for ultrasound to address important clinical challenges.

In this thesis, we explore the potential in engineering immune cells with various genetic elements which interact with either therapeutic or diagnostic ultrasound in novel ways. In Chapter 2, we engineer T-cells capable of sensing increases in temperature and responding by activating expression of therapeutic proteins to potentially increase safety of cell-based immunotherapies by controlling their spatiotemporal activation. In Chapters 3 and 4, we develop monocytes as ultrasound reporter cells for cancer detection by engineering them to express gas vesicles (GVs), a class of air-filled protein nanostructures natively found in certain aquatic microbes, which have been demonstrated to produce ultrasound contrast. We demonstrate the potential to confine GV expression to certain disease related signals to create ultrasound reporter cells. Together, these findings highlight the potential of engineering cells to activate in certain locations in response to ultrasound heating or serve as sentinel cells for disease detection.

Thesis Files