Insights into Photothermal Therapy-Derived Adoptive T Cells
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T cells, tumor cells, and dendritic cells (DCs). Throughout this work, the PTT-T cell platform is compared to T cells generated using three alternative tumor lysis methods
freeze-thaw, heat-induced, and oxidative lysis. Chapter two demonstrates that PTT-T cells display enhanced cytotoxicity, driven by a more activated and cytotoxic CD8⁺ T cell population. T cell receptor repertoire and transcriptomic analysis reveal clonal expansion of multitargeted, tumor-specific T cells. Chapter three characterizes the proteomic changes induced by PBNP-PTT, identifying damage-associated molecular patterns and cytokine profiles that may contribute to immunogenicity. Chapter four evaluates DCs primed with PTT-treated lysates, demonstrating comparable phenotypic characteristics but distinct antigen presentation profiles. Notably, the CD91 receptor mediates tumor-specific cytotoxicity in PTT-T cells but not freeze-thaw lysis-derived T cells. Together, these findings provide mechanistic insight into how PBNP-PTT tumor treatment promotes the generation of potent, tumor-specific T cells. This work supports the continued development of the PTT-T cell platform as a promising strategy for adoptive cell therapy in GBM.
Glioblastoma (GBM) remains one of the most aggressive and treatment-resistant central nervous system tumors, demanding innovative therapeutic strategies. This dissertation investigates the mechanisms underlying the efficacy of a novel adoptive T cell therapy platform generated using Prussian Blue nanoparticle-based photothermal therapy (PBNP-PTT) for the treatment of GBM. Prior studies have demonstrated the therapeutic potential of PBNP-PTT-derived T cells (PTT-T), including enhanced efficacy compared to freeze-thaw lysate-derived T cells. However, the biological basis for this enhanced activity remained unclear. To address this gap, this dissertation examines the roles of three key cellular components involved in the PTT-T cell generation
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