Development of In Vitro Assays for Advancing Radioimmunotherapy against Brain Tumors

Yohan Walter, Anne Hubbard, Allie Benoit, Erika Jank, Olivia Salas, Destiny Jordan, Andrew Ekpenyong

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number1796
JournalBiomedicines
Volume10
Issue number8
DOIs
StatePublished - Aug 2022

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

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