A combinational therapy of EGFR-CAR NK cells and oncolytic herpes simplex virus 1 for breast cancer brain metastases
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Author
Chen, Xilin
Han, Jianfeng
Chu, Jianhong
Zhang, Lingling
Zhang, Jianying
Chen, Charlie
Chen, Luxi
Wang, Youwei
Wang, Hongwei
Yi, Long
Elder, J. Bradley
Wang, Qi-En
He, Xiaoming
Kaur, Balveen
Yu, Jianhua
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.18632/oncotarget.8526Metadata
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Chen, X., J. Han, J. Chu, L. Zhang, J. Zhang, C. Chen, L. Chen, et al. 2016. “A combinational therapy of EGFR-CAR NK cells and oncolytic herpes simplex virus 1 for breast cancer brain metastases.” Oncotarget 7 (19): 27764-27777. doi:10.18632/oncotarget.8526. http://dx.doi.org/10.18632/oncotarget.8526.Abstract
Breast cancer brain metastases (BCBMs) are common in patients with metastatic breast cancer and indicate a poor prognosis. These tumors are especially resistant to currently available treatments due to multiple factors. However, the combination of chimeric antigen receptor (CAR)-modified immune cells and oncolytic herpes simplex virus (oHSV) has not yet been explored in this context. In this study, NK-92 cells and primary NK cells were engineered to express the second generation of EGFR-CAR. The efficacies of anti-BCBMs of EGFR-CAR NK cells, oHSV-1, and their combination were tested in vitro and in a breast cancer intracranial mouse model. In vitro, compared with mock-transduced NK-92 cells or primary NK cells, EGFR-CAR-engineered NK-92 cells and primary NK cells displayed enhanced cytotoxicity and IFN-γ production when co-cultured with breast cancer cell lines MDA-MB-231, MDA-MB-468, and MCF-7. oHSV-1 alone was also capable of lysing and destroying these cells. However, a higher cytolytic effect of EGFR-CAR NK-92 cells was observed when combined with oHSV-1 compared to the monotherapies. In the mice intracranially pre-inoculated with EGFR-expressing MDA-MB-231 cells, intratumoral administration of either EGFR-CAR-transduced NK-92 cells or oHSV-1 mitigated tumor growth. Notably, the combination of EGFR-CAR NK-92 cells with oHSV-1 resulted in more efficient killing of MDA-MB-231 tumor cells and significantly longer survival of tumor-bearing mice when compared to monotherapies. These results demonstrate that regional administration of EGFR-CAR NK-92 cells combined with oHSV-1 therapy is a potentially promising strategy to treat BCBMs.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053686/pdf/Terms of Use
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