The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
CAR-Engineered NK Cells Targeting Wild-Type EGFR and EGFRvIII Enhance Killing of Glioblastoma and Patient-Derived Glioblastoma Stem Cells
Open accessAbstract
Glioblastoma (GB) remains the most aggressive primary brain malignancy. Adoptive transfer of chimeric antigen receptor (CAR)-modified immune cells has emerged as a promising anti-cancer approach, yet the potential utility of CAR-engineered natural killer (NK) cells to treat GB has not been explored. Tumors from approximately 50% of GB patients express wild-type EGFR (wtEGFR) and in fewer cases express both wtEGFR and the mutant form EGFRvIII; however, previously reported CAR T cell studies only focus on targeting EGFRvIII. Here we explore whether both wtEGFR and EGFRvIII can be effectively targeted by CAR-redirected NK cells to treat GB. We transduced human NK cell lines NK-92 and NKL and primary NK cells with a lentiviral construct harboring a second generation CAR targeting both wtEGFR and EGFRvIII and evaluated the anti-GB efficacy of EGFR-CAR-modified NK cells. EGFR-CAR-engineered NK cells displayed enhanced cytolytic capability and IFN-γ production when co-cultured with GB cells or patient-derived GB stem cells in an EGFR-dependent manner. In two orthotopic GB xenograft mouse models, intracranial administration of NK-92-EGFR-CAR cells resulted in efficient suppression of tumor growth and significantly prolonged the tumor-bearing mice survival. These findings support intracranial administration of NK-92-EGFR-CAR cells represents a promising clinical strategy to treat GB.
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“[48] CAR construct containing CD28 co-stimulatory domain has also been developed to direct against HER2, [49] EGFR or EGFR variant III, [50] and CS1.”
BackgroundNatural killer cells in antitumour adoptive cell immunotherapy
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Metadata
- Authors
- Han, J., Chu, J., Keung Chan, W., Zhang, J., Wang, Y., Cohen, J. B., Victor, A., Meisen, W. H., Kim, S.-H., Grandi, P., Wang, Q.-E., He, X., Nakano, I., Chiocca, E. A., Glorioso III, J. C., Kaur, B., Caligiuri, M. A., & Yu, J.
- Venue
- Scientific Reports
- Published
- 2015-07-09
- Volume
- 5
- Issue
- 1
- Pages
- 11483-11483
- ISSN
- 2045-2322 (ISSN-L)
- OpenAlex
- W1800095175
- Cited by
- 340
- References
- 35
- FWCI
- 9.49
- Type
- journal article
- Language
- en
- Open access
- gold
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- Han, J., Chu, J., Keung Chan, W., Zhang, J., Wang, Y., Cohen, J. B., Victor, A., Meisen, W. H., Kim, S.-H., Grandi, P., Wang, Q.-E., He, X., Nakano, I., Chiocca, E. A., Glorioso III, J. C., Kaur, B., Caligiuri, M. A., & Yu, J. (2015). CAR-Engineered NK Cells Targeting Wild-Type EGFR and EGFRvIII Enhance Killing of Glioblastoma and Patient-Derived Glioblastoma Stem Cells. Scientific Reports. https://doi.org/10.1038/srep11483
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
