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

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

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

OriginalspracheEnglisch
Aufsatznummere08267
Seitenumfang14
FachzeitschriftAdvanced science
Jahrgang12
Ausgabenummer41
Frühes Online-Datum24 Juli 2025
PublikationsstatusVeröffentlicht - Nov. 2025
Peer-Review-StatusJa

Externe IDs

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

Schlagworte

Ziele für nachhaltige Entwicklung

Schlagwörter

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