CAR-neutrophil-mediated Drug Delivery Method for Treating Brain and Other Diseases

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Researchers at Purdue University have developed a method and use of a novel, targeted combinatorial chemo-immunotherapy against solid tumors like glioblastoma and other brain diseases. Glioblastoma (GBM) is one of the most aggressive and lethal solid tumors in humans. Neutrophil-mediated delivery of nanoparticulated chemotherapeutic drugs has been investigated due to their capacity to migrate toward inflamed sites and traverse the blood-brain barrier/blood-brain-tumor barrier (BBB/BBTB). However, the neutrophil recruitment therapy is limited owing to induction of additional inflammation via surgical resection of tumors. The Purdue researchers' therapy involves neutrophils differentiated from pluripotent stem cells and engineered to express GBM specific chimeric antigen receptor (CAR) and loaded with nanoparticles delivering the chemo-or radio-therapeutic drug. Internalization of the CAR-neutrophil-nanoparticle therapeutic leads to cytolysis and intracellular release of chemotherapeutic drugs after uptake by the tumor. The choice of CAR in the CAR-expressing neutrophils can be varied depending on the disease that is targeted. Depending on the targeted disease, the therapeutics can be administered intravenously or intratumorally.

Technology Validation: The combinatorial CAR-neutrophils loaded nanoparticle therapeutic efficiently killed tumor cells under various tumor niche-like conditions in vitro. Functional CAR-neutrophils were found to be biodistributed in the right forebrain of NRG mice and deliver nanodrugs to the tumor microenvironment.

Related Publication:

Engineering chimeric antigen receptor neutrophils from human pluripotent stem cells for targeted cancer immunotherapy. Chang et al., 2022, Cell Reports 40, 111128

CAR-neutrophil mediated delivery of tumor-microenvironment responsive nanodrugs for effective and safe glioblastoma chemoimmunotherapy. See PDF of the publication below

- GBM specific CAR-Neutrophil targeting minimizes off-target effects of Neutrophil based immunotherapy
- Drug delivery does not rely on post-surgery inflammatory signals.
- Therapeutic can be used with a treatment regime of chemotherapy or radiotherapy.
- Can be differentiated to treat brain and other diseases

- Treatment of glioblastoma, cancer, Alzheimer's disease, and other diseases
Oct 14, 2022
United States

Jun 14, 2022
United States
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