Purpose: Glioblastoma is the most common and malignant primary brain tumor. Due to factors including treatment resistance, local invasion, and high risk of recurrence, glioblastoma patient prognoses are often dismal, with median survival around 15 months. The standard of care consists of radiotherapy and concurrent or adjuvant chemotherapy with temozolomide (TMZ). However, patient survival has only marginally improved, calling for improved therapy for glioblastoma. Triumphs using anticancer agents acting as immune-checkpoint inhibitors against metastatic melanoma and non-small-cell lung cancer (NSCLC) have garnered interest toward applying these agents to glioblastoma. One agent, durvalumab, is undergoing phase I/II clinical trials in radioimmunotherapy for recurrent glioblastoma and high-grade glioma. However, agents showing high therapeutic potential may carry unforeseen effects which may affect treatment outcomes. The purpose of this work is to bring agents used in radioimmunotherapy to in vitro systems, where some effects may be better observed, with the goal of developing effective combination modalities for glioblastoma, which has a 5-10% 5-year survival rate.
Methods: Using a Faxitron CellRad cell irradiator and a commercially-available Electric Cell Impedance Sensor (ECIS), we quantified cell migration following the combination of radiotherapy and chemotherapy with TMZ, and now focus on the combination of radiotherapy and immunotherapy with durvalumab, a PD-L1 immune checkpoint inhibitor.
Results: Preliminary results show that irradiated T98-G and U87-MG cells (glioblastoma) migrate significantly more (p<0.01) than untreated cells in the first 20-40 hours posttreatment, and that concurrent temozolomide further alters migration and attachment. Shifting focus toward durvalumab in radioimmunotherapy, results in ECIS, cell morphometry, and clonogenic assays will be presented.
Conclusion: Our results suggest that ECIS can be used to explore effects of immunotherapy and radiotherapy on cell migration, aiding in determination of effective therapeutic windows for glioblastoma while detecting changes to cell behavior.