Tumor-Localized Control of CAR T Cells to Potentiate Solid Tumor Immunotherapy
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Zamat, Ali
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Abstract
Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of several hematological malignancies, achieving durable remissions in patients with B cell cancers. However, its efficacy against solid tumors remains limited due to challenges such as antigen heterogeneity, an immunosuppressive tumor microenvironment (TME), and the scarcity of tumor-specific antigens (TSAs). These obstacles not only impede T cell infiltration, activation, and persistence within tumors but also increase the risk of off-tumor toxicity due to the expression of tumor-associated antigens (TAAs) by healthy tissues. Addressing these barriers is crucial to unlock the full potential of CAR T cell therapy for solid tumor treatment. This thesis focuses on developing tumor-localized strategies to potentiate CAR T cell-mediated immunity against solid tumors.
I first develop thermal gene switches that enable remote control of gene expression in primary human and murine T cells in response to mild hyperthermia. By integrating
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2024-12-08
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Dissertation (PhD)