{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T11:07:31Z","timestamp":1786446451009,"version":"build-2736575974"},"reference-count":27,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T00:00:00Z","timestamp":1718236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T00:00:00Z","timestamp":1718236800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["HL125018"],"award-info":[{"award-number":["HL125018"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["AI124769"],"award-info":[{"award-number":["AI124769"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["AI129594"],"award-info":[{"award-number":["AI129594"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["AI130197"],"award-info":[{"award-number":["AI130197"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"name":"HHS | NIH | National Cancer Institute","award":["CA267368"],"award-info":[{"award-number":["CA267368"]}]},{"name":"New Jersey Commission on Cancer Research","award":["COCR24PRF004"],"award-info":[{"award-number":["COCR24PRF004"]}]},{"name":"HHS | NIH | National Cancer Institute","award":["CA227291"],"award-info":[{"award-number":["CA227291"]}]},{"name":"Anonymous private donor to The Ohio State University"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2024,6,13]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Recent progress on chimeric antigen receptor (CAR)-NK cells has shown promising results in treating CD19-positive lymphoid tumors with minimal toxicities [including graft versus host disease (GvHD) and cytokine release syndrome (CRS) in clinical trials. Nevertheless, the use of CAR-NK cells in combating viral infections has not yet been fully explored. Previous studies have shown that CAR-NK cells expressing S309 single-chain fragment variable (scFv), hereinafter S309-CAR-NK cells, can bind to SARS-CoV-2 wildtype pseudotyped virus (PV) and effectively kill cells expressing wild-type spike protein\n              <jats:italic>in vitro<\/jats:italic>\n              . In this study, we further demonstrate that the S309-CAR-NK cells can bind to different SARS-CoV-2 variants, including the B.1.617.2 (Delta), B.1.621 (Mu), and B.1.1.529 (Omicron) variants\n              <jats:italic>in vitro<\/jats:italic>\n              . We also show that S309-CAR-NK cells reduce virus loads in the NOD\/SCID gamma (NSG) mice expressing the human angiotensin-converting enzyme 2 (hACE2) receptor challenged with SARS-CoV-2 wild-type (strain USA\/WA1\/2020). Our study demonstrates the potential use of S309-CAR-NK cells for inhibiting infection by SARS-CoV-2 and for the potential treatment of COVID-19 patients unresponsive to otherwise currently available therapeutics.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>Chimeric antigen receptor (CAR)-NK cells can be \u201coff-the-shelf\u201d products that treat various diseases, including cancer, infections, and autoimmune diseases. In this study, we engineered natural killer (NK) cells to express S309 single-chain fragment variable (scFv), to target the Spike protein of SARS-CoV-2, hereinafter S309-CAR-NK cells. Our study shows that S309-CAR-NK cells are effective against different SARS-CoV-2 variants, including the B.1.617.2 (Delta), B.1.621 (Mu), and B.1.1.529 (Omicron) variants. The S309-CAR-NK cells can (i) directly bind to SARS-CoV-2 pseudotyped virus (PV), (ii) competitively bind to SARS-CoV-2 PV with 293T cells expressing the human angiotensin-converting enzyme 2 (hACE2) receptor (293T-hACE2 cells), (iii) specifically target and lyse A549 cells expressing the spike protein, and (iv) significantly reduce the viral loads of SARS-CoV-2 wild-type (strain USA\/WA1\/2020) in the lungs of NOD\/SCID gamma (NSG) mice expressing hACE2 (hACE2-NSG mice). Altogether, the current study demonstrates the potential use of S309-CAR-NK immunotherapy as an alternative treatment for COVID-19 patients.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/jvi.00038-24","type":"journal-article","created":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T13:01:29Z","timestamp":1716210089000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["S309-CAR-NK cells bind the Omicron variants\n            <i>in vitro<\/i>\n            and reduce SARS-CoV-2 viral loads in humanized ACE2-NSG mice"],"prefix":"10.1128","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5804-9155","authenticated-orcid":false,"given":"Minh Tuyet","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, South Orange Avenue, Newark, New Jersey, USA"},{"name":"School of Graduate Studies, Rutgers Biomedical and Health Sciences, Newark, New Jersey, USA"},{"name":"Center for Immunity and Inflammation, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0247-773X","authenticated-orcid":false,"given":"Qingkui","family":"Jiang","sequence":"additional","affiliation":[{"name":"Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Rutgers, The State University of New Jersey, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Hsiung","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, South Orange Avenue, Newark, New Jersey, USA"},{"name":"Center for Immunity and Inflammation, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2885-2315","authenticated-orcid":false,"given":"Saiaditya","family":"Badeti","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, South Orange Avenue, Newark, New Jersey, USA"},{"name":"School of Graduate Studies, Rutgers Biomedical and Health Sciences, Newark, New Jersey, USA"},{"name":"Center for Immunity and Inflammation, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9646-1051","authenticated-orcid":false,"given":"Xuening","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, South Orange Avenue, Newark, New Jersey, USA"},{"name":"Center for Immunity and Inflammation, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA"},{"name":"Center for Retrovirus Research, The Ohio State University, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Evans","sequence":"additional","affiliation":[{"name":"Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Rutgers, The State University of New Jersey, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany","family":"Bodnar","sequence":"additional","affiliation":[{"name":"Center for Metabolic Disease Research, Department of Pathology and Laboratory Medicine, Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2040-0354","authenticated-orcid":false,"given":"Salvatore A. 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