Authors:

Cillian Norton

Date Created:

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About Paper:

Glioblastoma (GBM) is a highly aggressive and malignant brain tumour with poor prognosis. While Chimeric Antigen Receptor (CAR) - T cells have demonstrated effective results in targeting certain forms of cancer, their success in treating glioblastoma tumours is greatly restricted by the Blood-Brain Barrier and Blood-Brain-Tumour Barriers. Neutrophils, which are innate immune cells capable of penetrating these barriers, already possess tumour-killing capabilities in the form of cytotoxic granules, reactive oxygen species and Neutrophil Extracellular Traps. As such, CAR-engineered neutrophils offer a potential new strategy for overcoming the limitations associated with CAR-T Cell Therapies. The clinical application of neutrophils has been limited due to their short lifespan and resistance to genetic modification. However, human pluripotent stem cell lines (hPSCs) offer a renewable source for generating neutrophils in vitro, allowing for genetic engineering and controlled differentiation. In this project, CAR-neutrophils were derived using engineered H9 hPSC lines using a chemically-defined cytokine- driven protocol. The resulting cells were characterised using molecular and cellular assays including flow cytometry analysis to confirm neutrophil-specific surface markers. Functional assays demonstrated that these CAR-neutrophils exhibit potent anti-tumour activity against GBM in-vitro. These findings suggest that CAR-neutrophils may provide an effective immunotherapy for the treatment of glioblastoma and potentially other severe diseases. Keywords: Neutrophil; Immunotherapy; Glioblastoma; Pluripotent Stem Cells

Source:

Purdue University / 2025

Topics:

No topics listed

Co-authors:

Cillian Norton