TY  - JOUR
AU  - Hunger, Jessica
AU  - Schregel, Katharina
AU  - Boztepe, Berin
AU  - Agardy, Dennis Alexander
AU  - Turco, Verena
AU  - Karimian-Jazi, Kianush
AU  - Weidenfeld, Ina
AU  - Streibel, Yannik
AU  - Fischer, Manuel
AU  - Sturm, Volker
AU  - Santarella-Mellwig, Rachel
AU  - Kilian, Michael
AU  - Jähne, Kristine
AU  - Sahm, Katharina
AU  - Wick, Wolfgang
AU  - Bunse, Lukas
AU  - Heiland, Sabine
AU  - Bunse, Theresa
AU  - Bendszus, Martin
AU  - Platten, Michael
AU  - Breckwoldt, Michael
TI  - In vivo nanoparticle-based T cell imaging can predict therapy response towards adoptive T cell therapy in experimental glioma.
JO  - Theranostics
VL  - 13
IS  - 15
SN  - 1838-7640
CY  - Wyoming, NSW
PB  - Ivyspring
M1  - DKFZ-2023-02220
SP  - 5170 - 5182
PY  - 2023
N1  - #EA:D170#LA:D170#
AB  - 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.
KW  - adoptive T cell therapy (Other)
KW  - glioma (Other)
KW  - immunotherapy (Other)
KW  - iron oxide nanoparticles (Other)
KW  - non-invasive treatment monitoring (Other)
KW  - tumor microenvironment (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:37908732
C2  - pmc:PMC10614679
DO  - DOI:10.7150/thno.87248
UR  - https://inrepo02.dkfz.de/record/285096
ER  -