In vivo nanoparticle-based T cell imaging can predict therapy response towards adoptive T cell therapy in experimental glioma

• Verfasst von: Hunger, Jessica [VerfasserIn]
• Verfasst von: Schregel, Katharina [VerfasserIn]
• Verfasst von: Boztepe, Berin [VerfasserIn]
• Verfasst von: Agardy, Dennis [VerfasserIn]
• Verfasst von: Turco, Verena [VerfasserIn]
• Verfasst von: Karimian-Jazi, Kianush [VerfasserIn]
• Verfasst von: Weidenfeld, Ina [VerfasserIn]
• Verfasst von: Streibel, Yannik [VerfasserIn]
• Verfasst von: Fischer, Manuel [VerfasserIn]
• Verfasst von: Sturm, Volker Jörg Friedrich [VerfasserIn]
• Verfasst von: Santarella-Mellwig, Rachel [VerfasserIn]
• Verfasst von: Kilian, Michael [VerfasserIn]
• Verfasst von: Jähne, Kristine [VerfasserIn]
• Verfasst von: Sahm, Katharina [VerfasserIn]
• Verfasst von: Wick, Wolfgang [VerfasserIn]
• Verfasst von: Bunse, Lukas [VerfasserIn]
• Verfasst von: Heiland, Sabine [VerfasserIn]
• Verfasst von: Bunse, Theresa [VerfasserIn]
• Verfasst von: Bendszus, Martin [VerfasserIn]
• Verfasst von: Platten, Michael [VerfasserIn]
• Verfasst von: Breckwoldt, Michael O. [VerfasserIn]
• Titel: In vivo nanoparticle-based T cell imaging can predict therapy response towards adoptive T cell therapy in experimental glioma
• Verf.angabe: Jessica Hunger, Katharina Schregel, Berin Boztepe, Dennis Alexander Agardy, Verena Turco, Kianush Karimian-Jazi, Ina Weidenfeld, Yannik Streibel, Manuel Fischer, Volker Sturm, Rachel Santarella-Mellwig, Michael Kilian, Kristine Jähne, Katharina Sahm, Wolfgang Wick, Lukas Bunse, Sabine Heiland, Theresa Bunse, Martin Bendszus, Michael Platten and Michael O. Breckwoldt
• E-Jahr: 2023
• Jahr: 2023.09.25
• Umfang: 13 S.
• Illustrationen: Illustrationen
• Fussnoten: Gesehen am 20.06.2024
• Titel Quelle: Enthalten in: Theranostics
• Ort Quelle: Wyoming, NSW : Ivyspring, 2011
• Jahr Quelle: 2023
• Band/Heft Quelle: 13(2023), 15, Seite 5170-5182
• ISSN Quelle: 1838-7640
• DOI: doi:10.7150/thno.87248
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1891935321

Abstract

Rationale: Intrinsic brain tumors, such as gliomas are largely resistant to immunotherapies including immune checkpoint blockade. Adoptive cell therapies (ACT) including chimeric antigen receptor (CAR) or T cell receptor (TCR)-transgenic T cell therapy targeting glioma-associated antigens are an emerging field in glioma immunotherapy. However, imaging techniques for non-invasive monitoring of adoptively transferred T cells homing to the glioma microenvironment are currently lacking. Methods: Ultrasmall iron oxide nanoparticles (NP) can be visualized non-invasively by magnetic resonance imaging (MRI) and dedicated MRI sequences such as T2* mapping. Here, we develop a protocol for efficient ex vivo labeling of murine and human TCR-transgenic and CAR T cells with iron oxide NPs. We assess labeling efficiency and T cell functionality by flow cytometry and transmission electron microscopy (TEM). NP labeled T cells are visualized by MRI at 9.4 T in vivo after adoptive T cell transfer and correlated with 3D models of cleared brains obtained by light sheet microscopy (LSM). Results: NP are incorporated into T cells in subcellular cytoplasmic vesicles with high labeling efficiency without interfering with T cell viability, proliferation and effector function as assessed by cytokine secretion and antigen-specific killing assays in vitro. We further demonstrate that adoptively transferred T cells can be longitudinally monitored intratumorally by high field MRI at 9.4 Tesla in a murine glioma model with high sensitivity. We find that T cell influx and homogenous spatial distribution of T cells within the TME as assessed by T2* imaging predicts tumor response to ACT whereas incomplete T cell coverage results in treatment resistance. Conclusion: This study showcases a rational for monitoring adoptive T cell therapies non-invasively by iron oxide NP in gliomas to track intratumoral T cell influx and ultimately predict treatment outcome.