(M0930-05-26) Advancing the Use of Chimeric Antigen Receptor T-cell Therapy (CAR T) in Glioblastoma Treatment

Purpose: Chimeric Antigen Receptor T-cell therapy (CAR T) has revolutionized cancer treatment yet faces challenges in effectively targeting Glioblastoma (GBM) due to its hypoxic microenvironment, which promotes immunosuppressive factors. This study aimed to investigate the potential of nanoparticles (NPs) and membranes to enhance CAR-T cell penetration into the GBM niche.

Methods: Using confocal microscopy for cell tracking and flow cytometry for CAR-T cell quantification in the brain chamber, we explored the impact of different materails on CAR-T cell infiltration.

Results: Inorganic gold NPs demonstrated the capacity to induce temporary leakage of Human Umbilical Vein Endothelial Cells (HUVEC) and Cancer-Associated Fibroblasts (CAF), facilitating CAR-T cell penetration. Organic BSA NPs exhibited enhanced CAR-T cell infiltration through interaction with ligand-receptor methods. Furthermore, asteocyte membrane-coated NPs showed promise in augmenting CAR-T cell penetration via homing effects.

Conclusion: This study highlights the potential of nanoparticle-based strategies to enhance the efficacy of CAR T-cell therapy for GBM by improving cellular penetration into the tumor microenvironment. These findings contribute to the development of innovative approaches to overcome the challenges associated with immunosuppressive environments in cancer therapy. Further research in this area could lead to the development of targeted therapies with improved outcomes for GBM patients.

Acknowledgements: This work was supported by the National Institutes of Health (NIH) MIRA R35GM133795 (P. Chen).


Figure 1. Integrated Platform for CAR-T Cell Infiltration Detection in the Brain
A) Cellular Layout of Blood-Brain-Barrier (BBB) Microfluidic Chip: The schematic representation illustrates the arrangement of cells within the BBB microfluidic chip.
B) Morphology and Design of BBB Chip: The image depicts the morphology of the BBB chip, with an insert highlighting its structural design.
C) Fluidic Connection of Microfluidic Chip: The diagram illustrates the interconnected fluidic pathways within the microfluidic chip, enabling the flow of fluids or particles.
In flow fusion, fluidic connections between different channels are established to facilitate fluid or particle flow.
D) Impact of Inorganic Nanoparticle Size on CAR-T Cell Penetration: The graph shows the effects of different sizes of inorganic nanoparticles on CAR-T cell penetration.