Microphysiological Solid Tumor Models in Hydrogel Beads for CAR T Cell Immunotherapy Evaluation
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
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 language | English |
|---|---|
| Article number | e08267 |
| Number of pages | 14 |
| Journal | Advanced science |
| Volume | 12 |
| Issue number | 41 |
| Early online date | 24 Jul 2025 |
| Publication status | Published - Nov 2025 |
| Peer-reviewed | Yes |
External IDs
| PubMed | 40704837 |
|---|---|
| Scopus | 105011850847 |
| ORCID | /0000-0003-2285-3621/work/189707741 |
| ORCID | /0000-0003-1010-2791/work/189708999 |
Keywords
Sustainable Development Goals
ASJC Scopus subject areas
Keywords
- Droplet microfluidics, Fibroblast activation protein, Immunotherapy, Micrometastases, PEGDA hydrogel beads, Tumor microenvironment, droplet microfluidics, micrometastases, immunotherapy, tumor microenvironment, fibroblast activation protein