Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Development of in Vitro Assays for Advancing Radioimmunotherapy Against Brain Tumors

Yohan Walter
ORCID logo ,
Anne Hubbard
,
Allie Benoit
,
Erika Jank
,
Olivia Salas
,
Destiny Jordan
,
Andrew Ekpenyong
* ORCID logo
Version 1 : Received: 7 May 2022 / Approved: 10 May 2022 / Online: 10 May 2022 (13:22:16 CEST)

A peer-reviewed article of this Preprint also exists.

Walter, Y.; Hubbard, A.; Benoit, A.; Jank, E.; Salas, O.; Jordan, D.; Ekpenyong, A. Development of In Vitro Assays for Advancing Radioimmunotherapy against Brain Tumors. Biomedicines 2022, 10, 1796. Walter, Y.; Hubbard, A.; Benoit, A.; Jank, E.; Salas, O.; Jordan, D.; Ekpenyong, A. Development of In Vitro Assays for Advancing Radioimmunotherapy against Brain Tumors. Biomedicines 2022, 10, 1796.

Abstract

Glioblastoma (GBM) is the most common primary brain tumor. Due to high resistance to treatment, local invasion, and 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 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 hours post-treatment. Addition of TMZ increased migration rates for T98G at the 20 Gy (p < 0.01). Neither TMZ nor durvalumab significantly changed cell survival in 21 days post-treatment. Interestingly, durvalumab abolished the enhanced migration effect, indicating possible potency against local invasion. These results provide parameters for rapid supplementary evaluation of RIT against brain tumors.

Keywords

glioblastoma; immunotherapy; radiotherapy; brain cancers; radioimmunotherapy; immune checkpoint inhibitors; temozolomide; durvalumab; immunoradiotherapy.

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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