TY  - JOUR
AU  - Peng, Xuan
AU  - Janićijević, Željko
AU  - Loureiro, Liliana R
AU  - Hoffmann, Lydia
AU  - Lee, Poh Soo
AU  - Cela, Isli
AU  - Kruppke, Benjamin
AU  - Kegler, Alexandra
AU  - Feldmann, Anja
AU  - Gorodetska, Ielizaveta
AU  - Markl, Anja Madleine
AU  - Dubrovska, Anna
AU  - Offermann, Anne Kathrin
AU  - Bachmann, Michael
AU  - Baraban, Larysa
TI  - Microphysiological Solid Tumor Models in Hydrogel Beads for CAR T Cell Immunotherapy Evaluation.
JO  - Advanced science
VL  - nn
SN  - 2198-3844
CY  - Weinheim
PB  - Wiley-VCH
M1  - DKFZ-2025-01536
SP  - nn
PY  - 2025
N1  - epub
AB  - 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.
KW  - PEGDA hydrogel beads (Other)
KW  - droplet microfluidics (Other)
KW  - fibroblast activation protein (Other)
KW  - immunotherapy (Other)
KW  - micrometastases (Other)
KW  - tumor microenvironment (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:40704837
DO  - DOI:10.1002/advs.202508267
UR  - https://inrepo02.dkfz.de/record/303117
ER  -