{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T10:59:10Z","timestamp":1788260350893,"version":"build-2803163510"},"reference-count":32,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T00:00:00Z","timestamp":1736294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kyverna Therapeutics","award":["M5-AF-WB_KYV-101"],"award-info":[{"award-number":["M5-AF-WB_KYV-101"]}]},{"name":"Lupus Research Alliance","award":["M5-AF-WB_KYV-101"],"award-info":[{"award-number":["M5-AF-WB_KYV-101"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and idiopathic inflammatory myositis (IIM) are autoimmune diseases managed with long-term immunosuppressive therapies. Hu19-CD828Z, a fully human anti-CD19 chimeric antigen receptor (CAR) with a CD28 costimulatory domain, is engineered to potently deplete B-cells. In this study, we manufactured Hu19-CD828Z CAR T-cells from peripheral blood of SLE, IIM, and SSc patients and healthy donors (HDs). CAR-mediated, CD19-specific activity of these cells was evaluated in vitro by assessing cytotoxicity, cytokine release, and proliferation assays in response to autologous CD19+ B-cells, the CD19+ NALM-6 B-cell line, or a CD19\u2212 U937 non-B-cell line as targets. The results demonstrated an increased proliferation of Hu19-CD828Z CAR T-cells and dose-dependent cytotoxicity against primary autologous and NALM-6 B-cells compared to non-transduced controls or co-cultures with non-B-cells. Notably, autoimmune-patient-derived CAR T-cells produced lower levels of inflammatory cytokines than healthy-donor-derived CAR T-cells in response to CD19+ B-cell targets. These data support the potential of Hu19-CD828Z and its therapeutic cell product KYV-101 as a therapeutic strategy to achieve deep B-cell depletion in SLE, IIM, and SSc patients, and highlights its promise for broader application in B-cell-driven autoimmune disorders.<\/jats:p>","DOI":"10.3390\/ijms26020467","type":"journal-article","created":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T07:40:13Z","timestamp":1736322013000},"page":"467","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Exploring CAR T-Cell Dynamics: Balancing Potent Cytotoxicity and Controlled Inflammation in CAR T-Cells Derived from Systemic Sclerosis and Myositis Patients"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2898-2112","authenticated-orcid":false,"given":"Janin","family":"Dingfelder","sequence":"first","affiliation":[{"name":"Department of Internal Medicine 5, Hematology and Oncology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen, 91054 Erlangen, Germany"},{"name":"Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen, 91054 Erlangen, Germany"},{"name":"Bavarian Cancer Research Center (BZKF), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jule","family":"Taubmann","sequence":"additional","affiliation":[{"name":"Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen, 91054 Erlangen, Germany"},{"name":"Department of Internal Medicine 3\u2014Rheumatology and Immunology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"von Heydebrand","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 5, Hematology and Oncology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen, 91054 Erlangen, Germany"},{"name":"Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen, 91054 Erlangen, Germany"},{"name":"Bavarian Cancer Research Center (BZKF), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Aigner","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 5, Hematology and Oncology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen, 91054 Erlangen, Germany"},{"name":"Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen, 91054 Erlangen, Germany"},{"name":"Bavarian Cancer Research Center (BZKF), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Bergmann","sequence":"additional","affiliation":[{"name":"Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen, 91054 Erlangen, Germany"},{"name":"Department of Internal Medicine 3\u2014Rheumatology and Immunology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9695-0657","authenticated-orcid":false,"given":"Johannes","family":"Knitza","sequence":"additional","affiliation":[{"name":"Institute for Digital Medicine, University Hospital Giessen-Marburg, Philipps University Marburg, 35043 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo","family":"Park","sequence":"additional","affiliation":[{"name":"Kyverna Therapeutics, Emeryville, CA 94608, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph K.","family":"Cheng","sequence":"additional","affiliation":[{"name":"Kyverna Therapeutics, Emeryville, CA 94608, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Van Blarcom","sequence":"additional","affiliation":[{"name":"Kyverna Therapeutics, Emeryville, CA 94608, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Schett","sequence":"additional","affiliation":[{"name":"Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen, 91054 Erlangen, Germany"},{"name":"Department of Internal Medicine 3\u2014Rheumatology and Immunology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Mackensen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 5, Hematology and Oncology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen, 91054 Erlangen, Germany"},{"name":"Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen, 91054 Erlangen, Germany"},{"name":"Bavarian Cancer Research Center (BZKF), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9648-2635","authenticated-orcid":false,"given":"Gloria","family":"Lutzny-Geier","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 5, Hematology and Oncology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen, 91054 Erlangen, Germany"},{"name":"Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen, 91054 Erlangen, Germany"},{"name":"Bavarian Cancer Research Center (BZKF), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1126\/science.aar6711","article-title":"CAR T cell immunotherapy for human cancer","volume":"359","author":"June","year":"2018","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1038\/s41577-018-0042-2","article-title":"CAR T cells for infection, autoimmunity and allotransplantation","volume":"18","author":"Maldini","year":"2018","journal-title":"Nat. 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