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@ARTICLE{Hunger:285096,
      author       = {J. Hunger$^*$ and K. Schregel and B. Boztepe$^*$ and D. A.
                      Agardy$^*$ and V. Turco$^*$ and K. Karimian-Jazi and I.
                      Weidenfeld and Y. Streibel and M. Fischer and V. Sturm and
                      R. Santarella-Mellwig and M. Kilian$^*$ and K. Jähne$^*$
                      and K. Sahm$^*$ and W. Wick$^*$ and L. Bunse$^*$ and S.
                      Heiland and T. Bunse$^*$ and M. Bendszus and M. Platten$^*$
                      and M. Breckwoldt$^*$},
      title        = {{I}n vivo nanoparticle-based {T} cell imaging can predict
                      therapy response towards adoptive {T} cell therapy in
                      experimental glioma.},
      journal      = {Theranostics},
      volume       = {13},
      number       = {15},
      issn         = {1838-7640},
      address      = {Wyoming, NSW},
      publisher    = {Ivyspring},
      reportid     = {DKFZ-2023-02220},
      pages        = {5170 - 5182},
      year         = {2023},
      note         = {#EA:D170#LA:D170#},
      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.},
      keywords     = {adoptive T cell therapy (Other) / glioma (Other) /
                      immunotherapy (Other) / iron oxide nanoparticles (Other) /
                      non-invasive treatment monitoring (Other) / tumor
                      microenvironment (Other)},
      cin          = {D170 / HD01 / B320},
      ddc          = {610},
      cid          = {I:(DE-He78)D170-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)B320-20160331},
      pnm          = {314 - Immunologie und Krebs (POF4-314)},
      pid          = {G:(DE-HGF)POF4-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37908732},
      pmc          = {pmc:PMC10614679},
      doi          = {10.7150/thno.87248},
      url          = {https://inrepo02.dkfz.de/record/285096},
}