Three-Dimensional Bioconjugated Liquid-Like Solid (LLS) Enhance Characterization of Solid Tumor - Chimeric Antigen...

Area of Science:

• Oncology
• Immunology
• Biotechnology

Background:

• Cancer immunotherapy shows promise, but effective preclinical models for studying tumor-immune interactions are lacking.
• Understanding these interactions is crucial for developing new therapeutic strategies against cancer.

Approach:

• Developed 3D confined microchannels using bio-conjugated liquid-like solids (LLS) to mimic the tumor microenvironment (TME).
• Utilized murine CD70-specific CAR T cells cocultured with CD70-expressing glioblastoma and osteosarcoma models.
• Employed long-term in situ imaging and single-cell transcriptomic profiling to analyze CAR T cell dynamics and anti-tumor activity.

Key Points:

• CAR T cells demonstrated efficient trafficking, infiltration, and killing of cancer cells within the 3D microchannels.
• Observed upregulation of cytokines and chemokines (IFNg, CXCL9, CXCL10, CCL2, CCL3, CCL4) indicating anti-tumor immune response.
• Identified cancer cells initiating an 'immune escape' response by invading the microenvironment upon immune attack, a phenomenon not seen in wild-type tumors.

Conclusions:

• 3D confined microchannels provide a viable platform for studying CAR T cell dynamics and anti-tumor functions in an immunosuppressive TME.
• This model facilitates the identification of differential gene expression in immune subpopulations and reveals cancer immune escape mechanisms.
• 3D in vitro platforms are essential for uncovering complex cancer immune biology, highlighting the importance of TME heterogeneity.