TMIC-18. Enhancing γδ T Cell Cytotoxicity Against Glioblastoma Multiforme Using Tyrosine Kinase Inhibitor

Abstract Glioblastoma Multiforme (GBM) is the most common primary malignant brain tumor, associated with poor prognosis and decreased quality of life. Recent developments in immunotherapy have provided promising treatment options for human cancer. Among them, several adoptive cell therapies are currently being studied for GBM treatment, such as chimeric antigen receptor (CAR) T cell therapy, CAR natural killer (NK) cells, natural killer T (NKT) cells, macrophages, dendritic cells, stem cell-based strategies, and gamma-delta T (γδ T) cells. γδ T cells are a rare subset of immune lymphocyte, accounting for around 0.5–5% of total lymphocytes in circulation, with unique γ and δ chain T-cell receptors (TCRs) and natural killer (NK) receptors, enabling them effective in immune surveillance against tumors and infections. However, previous studies have shown that GBM patients experience limited efficacy with γδ T cell adoptive cell therapy due to reduced immune cell activity or survival in the tumor microenvironment. Several clinically approved tyrosine kinase inhibitors (TKIs) have been shown not only to suppress tumor growth but also to enhance immune cell activity in patients. In this study, we investigated the effects of five FDA-approved TKIs on ex vivo expanded human γδ T cells. Among them, TKI-1 significantly increased the percentage of Vγ9Vδ2 (VD2) T cells, their fold expansion, expression of memory T cell markers, NK cell receptors, and cytotoxic activity against a glioblastoma (GBM) cell line. These findings highlight the potential of TKI-1 to boost γδ T cell function and cytotoxicity, presenting a promising strategy to improve adoptive cell therapy for cancer patients. This novel γδ T cell culture method has been filed as an invention patent in Taiwan (Application No. 114116792) and is currently under review.