Myeongsoo Kim

BioE Ph.D. Proposal Presentation

Time and Date: 3:00 – 5:00 PM, Monday, June 12, 2023

Location: UAW 3115 (McIntire Conference Room)

Zoom Link: https://gatech.zoom.us/j/98975142252

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. (Georgia Institute of Technology)
Younan Xia, Ph.D. (Georgia Institute of Technology)

Title: Cell nanoengineering with surface-conjugated nanoparticles for advanced adoptive cell therapy in solid tumor malignancies

Adoptive cell therapy (ACT) utilizes tumor-infiltrating lymphocytes (TILs) from cancer patients to target and eliminate cancer cells. This cell therapy has shown remarkable success in eradicating hematological tumors, like leukemias. However, its efficiency in treating solid malignancies has been limited due to the highly immunosuppressive tumor microenvironment. Additionally, patients receiving ACT may experience cytokine release syndrome, which can lead to widespread organ dysfunction. Therefore, there is a significant need to monitor the spatial and functional status of transferred TILs in real-time for optimizing current protocols of ACT in solid tumors. To address this need, I propose a strategy that synergistically combines ultrasound-guided photoacoustic (US/PA) imaging, nanotechnology, and cell engineering to enable real-time monitoring of ACT with high imaging contrast and longitudinal stability. US/PA imaging technique is non-invasive and provides anatomical and functional information with molecular specificity. Since naïve T cells produce negligible imaging contrast in US/PA imaging, labeling of T cells with exogenous PA contrast agents can greatly enhance the imaging contrast of transferred T cells in vivo. Consequently, this project aims to develop nanoparticle-labeled T cells for US/PA imaging-guided ACT and to assess immune responses of adoptive T cells using US/PA imaging. In Aim 1, I will synthesize and characterize exogenous contrast agents with a high PA response and excellent photostability to enable long-term monitoring of ACT with high imaging contrast. In Aim 2, I will devise a strategy to label T cells with these designed contrast agents, and then assess the functions of the labeled cells and their PA response. Moreover, I will monitor the trafficking of the nanoparticle-labeled T cells in the tumor site. In Aim 3, I will monitor the immune response of nanoparticle-labeled T cells to cancer cells in real-time. A successful outcome will contribute to a deeper understanding of the dynamic immune responses between transferred T cells and cancer cells, thereby facilitating clinical translation of ACT for solid tumor treatment and cancer characterization.