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标题：Expanded human NK cells armed with CAR uncouple potent anti-tumor activity from off-tumor toxicity against solid tumors
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作者：Ana L. Portillo ; Richard Hogg ; Sophie M. Poznanski 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：6
页码：1-20
DOI：10.1016/j.isci.2021.102619
语种：English
出版社：Elsevier
摘要：SummaryDespite the remarkable success of chimeric antigen receptor (CAR)-T cells against hematologic malignancies, severe off-tumor effects have constrained their use against solid tumors. Recently, CAR-engineered natural killer (NK) cells have emerged as an effective and safe alternative. Here, we demonstrate that HER2 CAR-expression in NK cells from healthy donors and patients with breast cancer potently enhances their anti-tumor functions against various HER2-expressing cancer cells, regardless of MHC class I expression. Moreover, HER2 CAR-NK cells exert higher cytotoxicity than donor-matched HER2 CAR-T cells against tumor targets. Importantly, unlike CAR-T cells, HER2 CAR-NK cells do not elicit enhanced cytotoxicity or inflammatory cytokine production against non-malignant human lung epithelial cells with basal HER2 expression. Further, HER2 CAR-NK cells maintain high cytotoxic function in the presence of immunosuppressive factors enriched in solid tumors. These results show that CAR-NK cells may be a highly potent and safe source of immunotherapy in the context of solid tumors.Graphical abstractDisplay OmittedHighlights•Primary HER2 CAR-NK cells from patients with cancer have potent anti-tumor functions•HER2 CAR-NK cells have a higher tumor killing capacity than HER2 CAR-T cells•HER2 CAR-NK cells are not overly activated against HER2+ lung epithelial cells•CAR-NK cells can overcome inhibition by the immunosuppressive factors TGF-β and PGE2Immunology; Cancer