Enhancing adoptive cell therapy: future strategies for immune cell radioprotection in neuro-oncology

Abstract Adoptive cell therapy (ACT), particularly chimeric antigen receptor T cell (CAR T) therapy, has emerged as a promising approach in cancer treatment, demonstrating efficacy in hematological malignancies but facing challenges in brain tumors. The combination of ACT with radiation therapy (RT)...

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Main Authors: Abigail J. Groth, Mustafa Khasraw, James D. Byrne, Zachary J. Reitman
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:npj Precision Oncology
Online Access:https://doi.org/10.1038/s41698-025-01059-5
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author Abigail J. Groth
Mustafa Khasraw
James D. Byrne
Zachary J. Reitman
author_facet Abigail J. Groth
Mustafa Khasraw
James D. Byrne
Zachary J. Reitman
author_sort Abigail J. Groth
collection DOAJ
description Abstract Adoptive cell therapy (ACT), particularly chimeric antigen receptor T cell (CAR T) therapy, has emerged as a promising approach in cancer treatment, demonstrating efficacy in hematological malignancies but facing challenges in brain tumors. The combination of ACT with radiation therapy (RT) offers a potential strategy to enhance therapeutic outcomes, as RT can stimulate immune responses by promoting antigen presentation and T cell recruitment. However, a major hurdle is the radiosensitivity of immune cells, leading to their rapid depletion within the radiation field, which undermines the benefits of this combination. This review explores strategies to increase the radioresistance of immune cells, highlighting the need for innovative radioprotective approaches. We discuss the potential of extremophile-derived molecules, such as the Damage Suppressor protein from tardigrades, as novel radioprotectants that could be integrated into ACT protocols. Furthermore, we address key considerations for clinical trial design, including the sequencing of RT and ACT, dosing parameters, and safety considerations. By bridging insights from extremophile biology and immuno-oncology, this work aims to optimize the efficacy of ACT in the challenging context of brain tumors, paving the way for enhanced treatment strategies in neuro-oncology.
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spelling doaj-art-3a41815d896643c3ba1b2c110738179c2025-08-20T03:42:29ZengNature Portfolionpj Precision Oncology2397-768X2025-07-019111410.1038/s41698-025-01059-5Enhancing adoptive cell therapy: future strategies for immune cell radioprotection in neuro-oncologyAbigail J. Groth0Mustafa Khasraw1James D. Byrne2Zachary J. Reitman3Department of Radiation Oncology, Duke University School of MedicineDepartment of Neurosurgery, Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical CenterDepartment of Radiation Oncology, University of IowaDepartment of Radiation Oncology, Duke University School of MedicineAbstract Adoptive cell therapy (ACT), particularly chimeric antigen receptor T cell (CAR T) therapy, has emerged as a promising approach in cancer treatment, demonstrating efficacy in hematological malignancies but facing challenges in brain tumors. The combination of ACT with radiation therapy (RT) offers a potential strategy to enhance therapeutic outcomes, as RT can stimulate immune responses by promoting antigen presentation and T cell recruitment. However, a major hurdle is the radiosensitivity of immune cells, leading to their rapid depletion within the radiation field, which undermines the benefits of this combination. This review explores strategies to increase the radioresistance of immune cells, highlighting the need for innovative radioprotective approaches. We discuss the potential of extremophile-derived molecules, such as the Damage Suppressor protein from tardigrades, as novel radioprotectants that could be integrated into ACT protocols. Furthermore, we address key considerations for clinical trial design, including the sequencing of RT and ACT, dosing parameters, and safety considerations. By bridging insights from extremophile biology and immuno-oncology, this work aims to optimize the efficacy of ACT in the challenging context of brain tumors, paving the way for enhanced treatment strategies in neuro-oncology.https://doi.org/10.1038/s41698-025-01059-5
spellingShingle Abigail J. Groth
Mustafa Khasraw
James D. Byrne
Zachary J. Reitman
Enhancing adoptive cell therapy: future strategies for immune cell radioprotection in neuro-oncology
npj Precision Oncology
title Enhancing adoptive cell therapy: future strategies for immune cell radioprotection in neuro-oncology
title_full Enhancing adoptive cell therapy: future strategies for immune cell radioprotection in neuro-oncology
title_fullStr Enhancing adoptive cell therapy: future strategies for immune cell radioprotection in neuro-oncology
title_full_unstemmed Enhancing adoptive cell therapy: future strategies for immune cell radioprotection in neuro-oncology
title_short Enhancing adoptive cell therapy: future strategies for immune cell radioprotection in neuro-oncology
title_sort enhancing adoptive cell therapy future strategies for immune cell radioprotection in neuro oncology
url https://doi.org/10.1038/s41698-025-01059-5
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