%0 Journal Article
%A Hunger, Jessica
%A Schregel, Katharina
%A Boztepe, Berin
%A Agardy, Dennis Alexander
%A Turco, Verena
%A Karimian-Jazi, Kianush
%A Weidenfeld, Ina
%A Streibel, Yannik
%A Fischer, Manuel
%A Sturm, Volker
%A Santarella-Mellwig, Rachel
%A Kilian, Michael
%A Jähne, Kristine
%A Sahm, Katharina
%A Wick, Wolfgang
%A Bunse, Lukas
%A Heiland, Sabine
%A Bunse, Theresa
%A Bendszus, Martin
%A Platten, Michael
%A Breckwoldt, Michael
%T In vivo nanoparticle-based T cell imaging can predict therapy response towards adoptive T cell therapy in experimental glioma.
%J Theranostics
%V 13
%N 15
%@ 1838-7640
%C Wyoming, NSW
%I Ivyspring
%M DKFZ-2023-02220
%P 5170 - 5182
%D 2023
%Z #EA:D170#LA:D170#
%X 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.
%K adoptive T cell therapy (Other)
%K glioma (Other)
%K immunotherapy (Other)
%K iron oxide nanoparticles (Other)
%K non-invasive treatment monitoring (Other)
%K tumor microenvironment (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:37908732
%2 pmc:PMC10614679
%R 10.7150/thno.87248
%U https://inrepo02.dkfz.de/record/285096