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@ARTICLE{Peng:303117,
      author       = {X. Peng and Ž. Janićijević and L. R. Loureiro and L.
                      Hoffmann and P. S. Lee and I. Cela and B. Kruppke and A.
                      Kegler and A. Feldmann and I. Gorodetska and A. M. Markl and
                      A. Dubrovska and A. K. Offermann and M. Bachmann$^*$ and L.
                      Baraban},
      title        = {{M}icrophysiological {S}olid {T}umor {M}odels in {H}ydrogel
                      {B}eads for {CAR} {T} {C}ell {I}mmunotherapy {E}valuation.},
      journal      = {Advanced science},
      volume       = {nn},
      issn         = {2198-3844},
      address      = {Weinheim},
      publisher    = {Wiley-VCH},
      reportid     = {DKFZ-2025-01536},
      pages        = {nn},
      year         = {2025},
      note         = {epub},
      abstract     = {Micrometastases are challenging to resect surgically and to
                      detect with in vivo imaging. Immunotherapy is highly
                      anticipated to revolutionize their treatment, but its
                      overall efficacy still remains limited for solid tumors.
                      Here, a 3D micrometastases model is developed to mimic key
                      microenvironmental cues, enabling in vitro evaluation of
                      chimeric antigen receptor (CAR) T cell immunotherapy.
                      Prostate cancer that preferentially metastasizes to, e.g.,
                      liver or bone marrow, is utilized as a model. Hydrogel beads
                      with an elastic modulus matching those of soft organs are
                      used to support long-term culturing, immunostaining, and
                      monitoring of the spheroids. As a biochemical cue, the
                      impact of fibroblast activation protein (FAP), an emerging
                      target in the tumor microenvironment, is investigated on
                      prostate cancer spheroids and on the efficacy of CAR T cell
                      therapy. The multi-spheroid model consists of prostate stem
                      cell antigen (PSCA)-expressing prostate cancer cells and
                      FAP-producing fibrosarcoma cells in varying ratios. The
                      morphological features of the model are compared to clinical
                      histopathology and metastatic murine model samples. Finally,
                      CAR T cell trials demonstrate successful chemoattraction and
                      infiltration through the hydrogel matrix, with a
                      dual-targeting approach against FAP and PSCA antigens
                      showing synergistic efficacy. This research provides
                      invaluable insights for engineering 3D tumor models and
                      modeling therapies targeting small metastatic or residual
                      tumors, suggesting that co-targeting may be a more effective
                      strategy to unlock the tumor microenvironment's
                      suppression.},
      keywords     = {PEGDA hydrogel beads (Other) / droplet microfluidics
                      (Other) / fibroblast activation protein (Other) /
                      immunotherapy (Other) / micrometastases (Other) / tumor
                      microenvironment (Other)},
      cin          = {DD01},
      ddc          = {624},
      cid          = {I:(DE-He78)DD01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40704837},
      doi          = {10.1002/advs.202508267},
      url          = {https://inrepo02.dkfz.de/record/303117},
}