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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,\n                    <jats:italic>e.g<\/jats:italic>\n                    ., 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\u2010term 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\u2010spheroid model consists of prostate stem cell antigen (PSCA)\u2010expressing prostate cancer cells and FAP\u2010producing 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\u2010targeting 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\u2010targeting may be a more effective strategy to unlock the tumor microenvironment's suppression.\n                  <\/jats:p>","DOI":"10.1002\/advs.202508267","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T13:16:10Z","timestamp":1753362970000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Microphysiological Solid Tumor Models in Hydrogel Beads for CAR T Cell Immunotherapy Evaluation"],"prefix":"10.1002","volume":"12","author":[{"given":"Xuan","family":"Peng","sequence":"first","affiliation":[{"name":"Helmholtz\u2010Zentrum Dresden\u2010Rossendorf Institute of Radiopharmaceutical Cancer Research  01328 Dresden Germany"},{"name":"Faculty of Medicine and University Hospital Carl Gustav Carus Technische 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