CAR-Engineered NK Cells Targeting Wild-Type EGFR and EGFRvIII Enhance Killing of Glioblastoma and Patient-Derived Glioblastoma Stem Cells
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Author
Han, Jianfeng
Chu, Jianhong
Keung Chan, Wing
Zhang, Jianying
Wang, Youwei
Cohen, Justus B.
Victor, Aaron
Meisen, Walter H.
Kim, Sung-hak
Grandi, Paola
Wang, Qi-En
He, Xiaoming
Nakano, Ichiro
Glorioso III, Joseph C.
Kaur, Balveen
Caligiuri, Michael A.
Yu, Jianhua
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/srep11483Metadata
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Han, J., J. Chu, W. Keung Chan, J. Zhang, Y. Wang, J. B. Cohen, A. Victor, et al. 2015. “CAR-Engineered NK Cells Targeting Wild-Type EGFR and EGFRvIII Enhance Killing of Glioblastoma and Patient-Derived Glioblastoma Stem Cells.” Scientific Reports 5 (1): 11483. doi:10.1038/srep11483. http://dx.doi.org/10.1038/srep11483.Abstract
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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496728/pdf/Terms of Use
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