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

Autor:	Hunger J; Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany.; Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Consortium (DKTK) within the German Cancer Research Center (DKFZ), Heidelberg, Germany., Schregel K; Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany., Boztepe B; Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany.; Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Consortium (DKTK) within the German Cancer Research Center (DKFZ), Heidelberg, Germany., Agardy DA; Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Consortium (DKTK) within the German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translational Neurosciences, Heidelberg University, Mannheim, Germany., Turco V; Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany.; Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Consortium (DKTK) within the German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translational Neurosciences, Heidelberg University, Mannheim, Germany., Karimian-Jazi K; Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany., Weidenfeld I; Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany., Streibel Y; Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany., Fischer M; Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany., Sturm V; Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany., Santarella-Mellwig R; European Molecular Biology Laboratory (EMBL), Heidelberg, Germany., Kilian M; Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Consortium (DKTK) within the German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translational Neurosciences, Heidelberg University, Mannheim, Germany., Jähne K; Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Consortium (DKTK) within the German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translational Neurosciences, Heidelberg University, Mannheim, Germany., Sahm K; Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Consortium (DKTK) within the German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translational Neurosciences, Heidelberg University, Mannheim, Germany., Wick W; Clinical Cooperation Unit Neurooncology, DKTK within DKFZ, Heidelberg, Germany.; Department of Neurology, National Center for Tumor Diseases (NCT), Heidelberg University Hospital, Heidelberg, Germany., Bunse L; Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Consortium (DKTK) within the German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translational Neurosciences, Heidelberg University, Mannheim, Germany., Heiland S; Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany., Bunse T; Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Consortium (DKTK) within the German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translational Neurosciences, Heidelberg University, Mannheim, Germany., Bendszus M; Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany., Platten M; Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Consortium (DKTK) within the German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translational Neurosciences, Heidelberg University, Mannheim, Germany.; DKFZ-Hector Cancer Institute at University Medical Center Mannheim, Mannheim, Germany., Breckwoldt MO; Neuroradiology Department, University Hospital Heidelberg, Heidelberg, Germany.; Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Consortium (DKTK) within the German Cancer Research Center (DKFZ), Heidelberg, Germany.
Jazyk:	angličtina
Zdroj:	Theranostics [Theranostics] 2023 Sep 25; Vol. 13 (15), pp. 5170-5182. Date of Electronic Publication: 2023 Sep 25 (Print Publication: 2023).
DOI:	10.7150/thno.87248
Abstrakt:	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 T 2 * 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 T 2 * 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. Competing Interests: Competing Interests: The authors have declared that no competing interest exists. (© The author(s).)
Databáze:	MEDLINE
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