In vivo nanoparticle-based T cell imaging can predict therapy response towards adoptive T cell therapy in experimental glioma
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 eme...
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| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2023.09.25
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| In: |
Theranostics
Year: 2023, Jahrgang: 13, Heft: 15, Pages: 5170-5182 |
| ISSN: | 1838-7640 |
| DOI: | 10.7150/thno.87248 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.7150/thno.87248 Verlag, lizenzpflichtig, Volltext: https://www.thno.org/v13p5170.htm 
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| Verfasserangaben: | 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 |
| Zusammenfassung: | 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. |
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| Beschreibung: | Gesehen am 20.06.2024 |
| Beschreibung: | Online Resource |
| ISSN: | 1838-7640 |
| DOI: | 10.7150/thno.87248 |