The DOI matches its Crossref record; 73 of the 73 references it cites were found in a registry or an index.
Human iPSC-Derived Natural Killer Cells Engineered with Chimeric Antigen Receptors Enhance Anti-tumor Activity
Open accessAbstract
Summary Chimeric antigen receptors (CARs) significantly enhance anti-tumor activity of immune effector cells. While most studies have evaluated CAR-expression in T cells, here we evaluate different CAR constructs that improve natural killer (NK) cell-mediated killing. We identified a CAR containing the transmembrane domain of NKG2D, the 2B4 co-stimulatory domain, and the CD3ζ signaling domain to mediate strong antigen-specific NK cell signaling. NK cells derived from human iPSCs that express this CAR (NK-CAR-iPSC-NK cells) have a typical NK cell phenotype and demonstrate improved anti-tumor activity compared to T-CAR expressing iPSC-derived NK cells (T-CAR-iPSC-NK cells) and non-CAR expressing cells. Using an ovarian cancer xenograft model, NK-CAR-iPSC-NK cells significantly inhibited tumor growth and prolonged survival compared to PB-NK cells, iPSC-NK cells, or T-CAR-iPSC-NK cells. Additionally, NK-CAR-iPSC-NK cells demonstrate similar in vivo activity as T-CAR-expressing T cells, though with less toxicity. These NK-CAR-iPSC-NK cells now provide standardized, targeted “off the shelf” lymphocytes for anti-cancer immunotherapy.
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Cites
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Up on the tightrope: natural killer cell activation and inhibition
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Debela, D. T., Muzazu, S. G., Heraro, K. D., Ndalama, M. T., Mesele, B. W., Haile, D. C., Kitui, S. K., & Manyazewal, T. (2021) · SAGE Open Medicine · doi:10.1177/20503121211034366 · Cited by 1,597
Harnessing innate immunity in cancer therapy
Demaria, O., Cornen, S., Daëron, M., Morel, Y., Medzhitov, R., & Vivier, E. (2019) · Nature · doi:10.1038/s41586-019-1593-5 · Cited by 957
Natural killer cells in cancer biology and therapy
Wu, S.-Y., Fu, T., Jiang, Y.-Z., & Shao, Z.-M. (2020) · Molecular Cancer · doi:10.1186/s12943-020-01238-x · Cited by 863
CAR-NK cells: A promising cellular immunotherapy for cancer
Xie, G., Dong, H., Liang, Y., Ham, J. D., Rizwan, R., & Chen, J. (2020) · eBioMedicine · doi:10.1016/j.ebiom.2020.102975 · Cited by 800
Natural killer cells in antitumour adoptive cell immunotherapy
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Metadata
- Authors
- Li, Y., Hermanson, D. L., Moriarity, B. S., & Kaufman, D. S.
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2018-08
- Volume
- 23
- Issue
- 2
- Pages
- 181-192.e5
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2810715813
- Cited by
- 981
- References
- 73
- FWCI
- 30.33
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Li, Y., Hermanson, D. L., Moriarity, B. S., & Kaufman, D. S. (2018). Human iPSC-Derived Natural Killer Cells Engineered with Chimeric Antigen Receptors Enhance Anti-tumor Activity. Cell Stem Cell. https://doi.org/10.1016/j.stem.2018.06.002
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