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Published on: April 16, 2019
Development of In Vitro Assays for Advancing Radioimmunotherapy against Brain Tumors
Yohan Walter1, Anne Hubbard1, Allie Benoit1
1Department of Physics, Creighton University, Omaha, NE 68178, USA.
Abstract:
Glioblastoma (GBM) is the most common primary brain tumor. Due to high resistance to treatment, local invasion, and a high risk of recurrence, GBM patient prognoses are often dismal, with median survival around 15 months. The current standard of care is threefold: surgery, radiation therapy, and chemotherapy with temozolomide (TMZ). However, patient survival has only marginally improved. Radioimmunotherapy (RIT) is a fourth modality under clinical trials and aims at combining immunotherapeutic agents with radiotherapy. Here, we develop in vitro assays for the rapid evaluation of RIT strategies. Using a standard cell irradiator and an Electric Cell Impedance Sensor, we quantify cell migration following the combination of radiotherapy and chemotherapy with TMZ and RIT with durvalumab, a PD-L1 immune checkpoint inhibitor. We measure cell survival using a cloud-based clonogenic assay. Irradiated T98G and U87 GBM cells migrate significantly (p < 0.05) more than untreated cells in the first 20−40 h post-treatment. Addition of TMZ increases migration rates for T98G at 20 Gy (p < 0.01). Neither TMZ nor durvalumab significantly change cell survival in 21 days post-treatment. Interestingly, durvalumab abolishes the enhanced migration effect, indicating possible potency against local invasion. These results provide parameters for the rapid supplementary evaluation of RIT against brain tumors.
Insights
Radioimmunotherapy (RIT) combined with durvalumab may combat glioblastoma (GBM) local invasion. This study developed rapid in vitro assays to evaluate RIT strategies, showing durvalumab can reduce treatment-induced GBM cell migration.
Area of Science:
- Neuro-oncology
- Radiation oncology
- Immunotherapy
Background:
- Glioblastoma (GBM) presents dismal prognoses due to treatment resistance, local invasion, and recurrence.
- Current standard care (surgery, radiation, temozolomide) offers marginal survival improvement.
- Radioimmunotherapy (RIT) is an emerging fourth modality combining immunotherapy with radiotherapy.
Purpose of the Study:
- To develop rapid in vitro assays for evaluating RIT strategies in GBM.
- To quantify GBM cell migration and survival following combined radiotherapy, chemotherapy, and RIT.
Main Methods:
- Utilized Electric Cell Impedance Sensing (ECIS) to measure GBM cell migration.
- Employed a cloud-based clonogenic assay to assess cell survival.
- Evaluated the effects of radiotherapy, temozolomide (TMZ), and durvalumab (anti-PD-L1) on T98G and U87 GBM cells.
Main Results:
- Irradiated GBM cells showed significantly increased migration post-treatment.
- Temozolomide (TMZ) further enhanced migration in T98G cells at 20 Gy.
- Durvalumab abolished the enhanced migration, suggesting potential to inhibit local invasion.
- Neither TMZ nor durvalumab significantly impacted cell survival over 21 days.
Conclusions:
- Developed rapid in vitro assays for supplementary evaluation of RIT in brain tumors.
- Durvalumab shows potential in mitigating treatment-induced GBM cell migration, a key aspect of local invasion.
- Further investigation into RIT with durvalumab for GBM is warranted.
