Abstract 2187: Kinetics and potency of T Cell-mediated cytolysis of glioblastoma

Glioblastoma (GBM) is an aggressive form of brain cancer that has no effective treatments and a prognosis of only 12-15 months. Immune system effector T cells are a promising therapy due to their high specificity and innate cytotoxicity. The ability to assess the efficacy and potency of T cell therapies in vitro and with high throughput is vital for the further development of this promising therapy. Cellular impedance-based assays offer a sensitive, label-free, and nondestructive method to continuously monitor cancer cell proliferation and immune cell-mediated cytotoxicity in real-time and at high throughputs, revealing not only the potency but also the kinetics of T cell therapies. Here, we investigated the targeting potency of activated human T cells on human U87MG glioma cell monolayers across multiple cell densities. U87MG cells were plated at 10k, 25k, and 50k cells per well on a PDL-coated CytoView-Z 96-well plate (n=12 wells per density), and their impedance was continuously monitored on the Maestro Z impedance platform. After 24 hours, activated patient-derived T Cells (ImmunoCult CD3/CD28 activation media) were added in a 10:1 effector:target ratio. Impedance and cytolysis were subsequently monitored for another 120 hours. As expected, higher densities proliferated faster and reached a higher impedance level at 24 hours. The addition of activated human T cells resulted in a decrease of the impedance signal consistent with T cell-mediated lysis of the glioma cells. The highest density of T cells (500k) exhibited the fastest rate of U87 cytolysis, with a Kill Time 50 of 35 hours. All densities reached 100% cytolysis by 100 hours. Overall, activated human T cells were highly effective for cytolysis of U87MG glioma cell monolayers of varying densities. The cellular impedance assay revealed high potency, with kinetics that varied across cell densities despite the same effector:target ratios. Citation Format: Stacie A. Chvatal, Meghan T. Logun, Heather B. Hayes, Daniel C. Millard, Lohitash Karumbaiah. Kinetics and potency of T Cell-mediated cytolysis of glioblastoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2187.