Engineering chimeric antigen receptor neutrophils from human pluripotent stem cells for targeted cancer immunotherapy
- Cell Rep. 2022 Jul 19;40(3):111128. doi: 10.1016/j.celrep.2022.111128.
- 1. Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN 47907, USA; Purdue University Center for Cancer Research, West Lafayette, IN 47907, USA.
- 2. Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
- 3. Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
- 4. Purdue University Center for Cancer Research, West Lafayette, IN 47907, USA.
- 5. Purdue University Center for Cancer Research, West Lafayette, IN 47907, USA; Department of Comparative Pathobiology, Purdue University, West Lafayette, IN 47907, USA.
- 6. Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN 47907, USA.
- 7. Department of Biomedical Engineering, The Huck Institutes of the Life Sciences, Department of Biology, The Pennsylvania State University, University Park, PA 16802, USA. Electronic address: [email protected].
- 8. Purdue University Center for Cancer Research, West Lafayette, IN 47907, USA; Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA. Electronic address: [email protected].
- 9. Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN 47907, USA; Purdue University Center for Cancer Research, West Lafayette, IN 47907, USA. Electronic address: [email protected].
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 present 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.