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Glioblastoma, an aggressive form of cancer affecting the brain or spinal cord, is difficult to treat and has low survival rates. Surgical removal can be dangerous and the tumors have a tendency to regrow. About 14,000 cases of glioblastoma are diagnosed in the United States annually. Neutrophils are the most abundant white blood cell type, can infiltrate solid tumors and have shown superior antitumor activity against glioblastomas and blood diseases, but have a prohibitively short shelf life and are difficult to produce in sufficient quantities.
Purdue researchers have developed a method to mass-produce CAR-neutrophils with chimeric antigen receptors in 20% larger volume and 30% lower cost than traditional methods. This technology could advance quality of life when treating glioblastomas or accelerate additional research into cell therapy usage on other diseases.
IN THE MEDIA
Purdue University News Release
This research project was partially supported by the Davidson School of Chemical Engineering and College of Engineering Startup Funds, Purdue Center for Cancer Research, Showalter Research Trust and federal grants from the National Science Foundation and National Institute of General Medical Sciences.
Xiaoping Bao, Purdue University assistant professor from the Davidson School of Chemical Engineering
Human Chimeric Antigen Receptor (CAR) Neutrophils to Treat Cancer: 2021-BAO-69243
Phone: (765) 588-3475
Fax: (765) 463-3486
Engineering chimeric antigen receptor neutrophils from human pluripotent stem cells for targeted cancer immunotherapy
Yun Chang, Ramizah Syahirah, Xuepeng Wang, Gyuhyung Jin, Sandra Torregrosa-Allen, Bennett D. Elzey, Sydney N. Hummel, Tianqi Wang, Can Li, Xiaojun Lian, Qing Deng, Hal E. Broxmeyer, Xiaoping Bao
Neutrophils, the most abundant white blood cells in circulation, are closely related to cancer development and progression. Healthy primary neutrophils present potent cytotoxicity against various cancer cell lines through direct contact and via generation of reactive oxygen species. However, due to their short half-life and resistance to genetic modification, neutrophils have not yet been engineered with chimeric antigen receptors (CARs) to enhance their antitumor cytotoxicity for targeted immunotherapy. Here, we genetically engineered human pluripotent stem cells with synthetic CARs and differentiated them into functional neutrophils by implementing a chemically-defined platform. The resulting CAR-neutrophils presented superior and specific cytotoxicity against tumor cells both in vitro and in vivo. Collectively, we established a robust platform for massive production of CAR-neutrophils, paving the way to myeloid cell-based therapeutic strategies that would boost current cancer treatment approaches.