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

Area of Science:

• Biomedical Engineering
• Cancer Research
• Immunotherapy

Background:

• Micrometastases pose challenges for surgical resection and in vivo imaging.
• Immunotherapy efficacy for solid tumors remains limited.
• The tumor microenvironment significantly impacts treatment outcomes.

Purpose of the Study:

• To develop a 3D micrometastasis model for in vitro evaluation of CAR T cell immunotherapy.
• To investigate the role of fibroblast activation protein (FAP) in prostate cancer micrometastases and CAR T cell therapy.
• To assess the efficacy of a dual-targeting strategy against FAP and PSCA.

Main Methods:

• A 3D hydrogel bead-based micrometastasis model was created using prostate cancer cells and FAP-producing fibrosarcoma cells.
• The model mimicked soft organ elasticity and incorporated FAP as a biochemical cue.
• Chimeric antigen receptor (CAR) T cell therapy was evaluated in vitro, including a dual-targeting approach.

Main Results:

• The 3D model successfully replicated key microenvironmental cues and morphological features of clinical samples.
• CAR T cells demonstrated chemoattraction and infiltration within the hydrogel matrix.
• Dual targeting of FAP and PSCA antigens exhibited synergistic efficacy, overcoming tumor microenvironment suppression.

Conclusions:

• The developed 3D micrometastasis model is valuable for engineering and evaluating therapies against small metastatic or residual tumors.
• Co-targeting FAP and PSCA antigens represents a promising synergistic strategy for enhancing immunotherapy efficacy.
• This research offers insights into overcoming tumor microenvironment-mediated resistance in cancer treatment.