Microphysiological Solid Tumor Models in Hydrogel Beads for CAR T Cell Immunotherapy Evaluation

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Xuan Peng - , National Center for Tumor Diseases Dresden, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), University Hospital Carl Gustav Carus Dresden (Author)
  • Zeljko Janicijevic - , Helmholtz-Zentrum Dresden-Rossendorf (HZDR) (Author)
  • Liliana R. Loureiro - , Helmholtz-Zentrum Dresden-Rossendorf (HZDR) (Author)
  • Lydia Hoffmann - , Helmholtz-Zentrum Dresden-Rossendorf (HZDR) (Author)
  • Poh Soo Lee - , Chair of Biomaterials, Max Bergmann Center of Biomaterials Dresden (Author)
  • Isli Cela - , Helmholtz-Zentrum Dresden-Rossendorf (HZDR) (Author)
  • Benjamin Kruppke - , Chair of Biomaterials, Max Bergmann Center of Biomaterials Dresden (Author)
  • Alexandra Kegler - , Helmholtz-Zentrum Dresden-Rossendorf (HZDR) (Author)
  • Anja Feldmann - , Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Medical Faculty Carl Gustav Carus (Author)
  • Ielizaveta Gorodetska - , OncoRay - National Center for Radiation Research in Oncology, University Hospital Carl Gustav Carus Dresden (Author)
  • Anja Madleine Markl - , Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Medical Faculty Carl Gustav Carus, OncoRay - National Centre for Radiation Research in Oncology (Author)
  • Anna Dubrovska - , OncoRay - National Center for Radiation Research in Oncology, University Hospital Carl Gustav Carus Dresden (Author)
  • Anne Kathrin Offermann - , University Hospital Münster (Author)
  • Michael Bachmann - , Institute for Immunology, National Center for Tumor Diseases Dresden, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), University Hospital Carl Gustav Carus Dresden, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK) Partner Site Dresden (Author)
  • Larysa Baraban - , Else Kröner Fresenius Center for Digital Health, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), University Hospital Carl Gustav Carus Dresden (Author)

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.

Details

Original languageEnglish
Article numbere08267
Number of pages14
JournalAdvanced science
Volume12
Issue number41
Early online date24 Jul 2025
Publication statusPublished - Nov 2025
Peer-reviewedYes

External IDs

PubMed 40704837
Scopus 105011850847
ORCID /0000-0003-2285-3621/work/189707741
ORCID /0000-0003-1010-2791/work/189708999

Keywords

Sustainable Development Goals

Keywords

  • Droplet microfluidics, Fibroblast activation protein, Immunotherapy, Micrometastases, PEGDA hydrogel beads, Tumor microenvironment, droplet microfluidics, micrometastases, immunotherapy, tumor microenvironment, fibroblast activation protein