Myeongsoo Kim

Bioengineering PhD Defense Presentation

November 25 (Tuesday), 2025

12:00 PM

Location: Molecular Science and Engineering Building (MOSE) 3201A

Meeting link: https://gatech.zoom.us/j/98339800746

Advisor:  Stanislav Emelianov, Ph.D. (Georgia Institute of Technology)

Committee:
Vida Jamali, Ph.D. (Georgia Institute of Technology)
Ravi Kane, Ph.D. (Georgia Institute of Technology)
Gabriel A. Kwong, Ph.D. (Georgia Institute of Technology)
Krishnendu Roy, Ph. D. (Vanderbilt University)
Younan Xia, Ph.D. (Georgia Institute of Technology)

Noninvasive monitoring of antitumor activity of T cells via plasmonic photoacoustic nanosensors

Adoptive T cell therapy (ACT) is a promising strategy for cancer treatment that harnesses a patient’s own T lymphocytes to enhance antitumor immunity. A major challenge in assessing therapeutic responses following ACT is the lack of robust, noninvasive tools to monitor antitumor T cell activity with anatomical context. This thesis presents an integrated strategy for noninvasive, longitudinal monitoring of ACT using plasmonic gold nanoconstructs in combination with ultrasound-guided photoacoustic (US/PA) imaging as follows: (1) We developed semi-connected gold nanoassemblies (GNAs) by tuning interparticle connectivity of gold nanospheres inside a polymer layer to enhance near-infrared (NIR) light absorption, photostability, and PA responses. This study demonstrates that interparticle coupling in gold nanoconstructs directly influences imaging contrast and signal reliability over repeated imaging sessions. (2) Building on this GNA design, we extended the platform toward functional monitoring of T cell immunotherapy. Membrane-bound GNAs on CAR T cells enable noninvasive, longitudinal PA imaging of T cells in heterogeneous solid tumors.  Longitudinal PA imaging revealed a correlation between early T cell trafficking and tumor responses. (3) Protease-activated plasmonic nanosensors were developed to detect granzyme B (GzmB), a key T cell effector protease. Upon exposure to GzmB, nanosensor aggregation is induced, leading to enhanced NIR light absorption. This significantly amplifies PA signals, enabling sensitive detection of GzmB with specificity. In murine ACT models, systemic nanosensor administration enables detection of tumor-infiltrating cytotoxic T cell activity, producing elevated PA signals in antigen-positive tumors compared to antigen-negative controls before measurable differences in tumor volume. Overall, this thesis demonstrates that the integration of plasmonic nanosensors with US/PA imaging not only advances the understanding of T cell-mediated antitumor responses but also provides a real-time monitoring platform to assess and potentially predict therapeutic outcomes in cancer immunotherapies.