Off-the-shelf CAR natural killer cells secreting IL-15 target spike in treating COVID-19.

Autor: Lu T; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA.; Hematologic Malignancies Research Institute, City of Hope National Medical Center, Los Angeles, CA, 91010, USA., Ma R; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA., Dong W; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA., Teng KY; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA., Kollath DS; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA., Li Z; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA., Yi J; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA., Bustillos C; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA., Ma S; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA., Tian L; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA., Mansour AG; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA., Li Z; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA., Settles EW; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA., Zhang J; Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Los Angeles, CA, 91010, USA., Keim PS; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA.; Division of Pathogen and Microbiome, TGen North, Flagstaff, AZ, 86011, USA., Barker BM; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA., Caligiuri MA; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA. mcaligiuri@coh.org.; Hematologic Malignancies Research Institute, City of Hope National Medical Center, Los Angeles, CA, 91010, USA. mcaligiuri@coh.org.; City of Hope Comprehensive Cancer Center, Los Angeles, CA, 91010, USA. mcaligiuri@coh.org., Yu J; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA. jiayu@coh.org.; Hematologic Malignancies Research Institute, City of Hope National Medical Center, Los Angeles, CA, 91010, USA. jiayu@coh.org.; City of Hope Comprehensive Cancer Center, Los Angeles, CA, 91010, USA. jiayu@coh.org.; Department of Immuno-Oncology, Beckman Research Institute of City of Hope, Los Angeles, CA, 91010, USA. jiayu@coh.org.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 May 11; Vol. 13 (1), pp. 2576. Date of Electronic Publication: 2022 May 11.
DOI: 10.1038/s41467-022-30216-8
Abstrakt: Engineered natural killer (NK) cells represent a promising option for immune therapy option due to their immediate availability in allogeneic settings. Severe acute diseases, such as COVID-19, require targeted and immediate intervention. Here we show engineering of NK cells to express (1) soluble interleukin-15 (sIL15) for enhancing their survival and (2) a chimeric antigen receptor (CAR) consisting of an extracellular domain of ACE2, targeting the spike protein of SARS-CoV-2. These CAR NK cells (mACE2-CAR_sIL15 NK cells) bind to VSV-SARS-CoV-2 chimeric viral particles as well as the recombinant SARS-CoV-2 spike protein subunit S1 leading to enhanced NK cell production of TNF-α and IFN-γ and increased in vitro and in vivo cytotoxicity against cells expressing the spike protein. Administration of mACE2-CAR_sIL15 NK cells maintains body weight, reduces viral load, and prolongs survival of transgenic mice expressing human ACE2 upon infection with live SARS-CoV-2. These experiments, and the capacity of mACE2-CAR_sIL15 NK cells to retain their activity following cryopreservation, demonstrate their potential as an allogeneic off-the-shelf therapy for COVID-19 patients who are faced with limited treatment options.
(© 2022. The Author(s).)
Databáze: MEDLINE
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