Expanded human NK cells armed with CAR uncouple potent anti-tumor activity from off-tumor toxicity against solid tumors

Autor: Ana L. Portillo, Richard Hogg, Sophie M. Poznanski, Eduardo A. Rojas, Niamh J. Cashell, Joanne A. Hammill, Marianne V. Chew, Mira M. Shenouda, Tyrah M. Ritchie, Quynh T. Cao, Jeremy A. Hirota, Sukhbinder Dhesy-Thind, Jonathan L. Bramson, Ali A. Ashkar
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: iScience, Vol 24, Iss 6, Pp 102619- (2021)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2021.102619
Popis: Summary: Despite 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.
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