{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:27:23Z","timestamp":1788456443171,"version":"build-2803163510"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"abstract":"\n Background:<\/jats:title>\n CAR T cell therapy has revolutionized the treatment of hematological malignancies by effectively eliminating tumor cells. In the field of kidney transplantation, comparable cellular therapies are being explored to facilitate transplantation and prevent graft rejection. Chimeric HLA antibody receptor (CHAR) T cells are a promising therapy for eliminating HLA-specific B cells in sensitized patients and potentially ameliorating antibody-mediated rejection. We previously demonstrated that HLA class I CHAR T cells selectively eliminated HLA class I-specific B cells with high specificity. Since HLA sensitization is most often directed against HLA-DQ of the allograft, we developed HLA-DQ2 and HLA-DQ7 CHAR T cells to target B cells with corresponding HLA specificity.<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n \n We designed viral vectors encoding HLA-DQ CHARs composed of HLA-DQA1*05:01 alpha chain with either HLA-DQB1*02:01 (HLA-DQ2) or HLA-DQB1*03:01 (HLA-DQ7) beta chains, CLIP peptide, and intracellular 4-1BB costimulatory and CD3\u03b6 signaling domains. Upon production of HLA-DQ CHAR T cells, we evaluated CHAR expression, cytotoxic activity, production of cytokines and cytotoxic mediators, and sensitivity to immunosuppressive drugs in\n in vitro<\/jats:italic>\n models. We further assessed the cytotoxic activity of HLA-DQ CHAR T cells in an immunodeficient mouse model and in primary material from sensitized individuals.\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n CHAR-transduced Jurkat Triple Parameter Reporter (Jurkat\n TPR<\/jats:sup>\n ) cells expressing reporter constructs for T cell activation markers showed robust activation upon specific stimulation. Primary CD8\n +<\/jats:sup>\n T cells expressing HLA-DQ2 and HLA-DQ7 CHAR molecules specifically eliminated HLA-DQ2- or HLA-DQ7-specific B cells, respectively, and produced interferon gamma, soluble Fas ligand, perforin, and granzyme B. Maintenance immunosuppressive drug regimens initiated at the time of co-incubation with target cells had limited effects on CHAR T-cell functionality. Finally, HLA-DQ CHAR T cells effectively eliminated HLA-DQ-specific B cells in an\n in vivo<\/jats:italic>\n mouse model, as well as in primary material from sensitized individuals.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n \n HLA-DQ2 and HLA-DQ7 CHAR T cells, the first HLA class II CHAR T cells, selectively and effectively eliminated corresponding HLA-DQ-specific B cells\n in vitro<\/jats:italic>\n ,\n in vivo<\/jats:italic>\n , and in primary material from sensitized individuals.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.0000001244","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:00:25Z","timestamp":1788454825000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Chimeric HLA Antibody Receptor (CHAR) T Cells to Specifically Eliminate HLA-DQ\u2013Specific B Cells"],"prefix":"10.1681","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1100-5758","authenticated-orcid":false,"given":"Carolt","family":"Arana","sequence":"first","affiliation":[{"name":"Hospital Cl\u00ednic Barcelona, Nephrology and Kidney Transplantation, Barcelona, Spain,"},{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Barcelona, Spain."},{"name":"Faculty of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0297-1743","authenticated-orcid":false,"given":"Ilse","family":"Gille","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center, Department of Immunology, Leiden, Netherlands."},{"name":"Leiden University Medical Center, Department of Hematology, Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renate","family":"Hagedoorn","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center, Department of Hematology, Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5968-0256","authenticated-orcid":false,"given":"Ainhoa","family":"Garc\u00eda-Busquets","sequence":"additional","affiliation":[{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Barcelona, Spain."},{"name":"Faculty of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7561-1353","authenticated-orcid":false,"given":"Hannah C.M.","family":"Schenk","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center, Department of Hematology, Leiden, Netherlands."},{"name":"Erasmus Medical Center, Department of Internal Medicine, Rotterdam, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4199-1168","authenticated-orcid":false,"given":"Sergi","family":"Betriu","sequence":"additional","affiliation":[{"name":"Hospital Cl\u00ednic Barcelona, Department of Immunology, Barcelona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0547-0975","authenticated-orcid":false,"given":"Dennis F. G.","family":"Remst","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center, Department of Hematology, Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen M.W.","family":"van der Meer-Prins","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center, Department of Immunology, Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2961-9360","authenticated-orcid":false,"given":"Yvonne J.H. de","family":"Vaal","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center, Department of Immunology, Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim H.","family":"Voogt-Bakker","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center, Department of Immunology, Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rico","family":"Buchli","sequence":"additional","affiliation":[{"name":"HLA Protein Technologies Inc, Oklahoma, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9284-3595","authenticated-orcid":false,"given":"Aiko P.J.","family":"de Vries","sequence":"additional","affiliation":[{"name":"Leiden Transplant Center; and Department of Internal Medicine, Division of Nephrology, Leiden University Medical Center, Leiden University, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3064-1648","authenticated-orcid":false,"given":"Manel","family":"Juan","sequence":"additional","affiliation":[{"name":"Hospital Cl\u00ednic Barcelona, Department of Immunology, Barcelona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1350-2336","authenticated-orcid":false,"given":"Cynthia S.M.","family":"Kramer","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center, Department of Immunology, Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1544-1485","authenticated-orcid":false,"given":"Eduard","family":"Palou","sequence":"additional","affiliation":[{"name":"Hospital Cl\u00ednic Barcelona, Department of Immunology, Barcelona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1846-1193","authenticated-orcid":false,"given":"Dave L.","family":"Roelen","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center, Department of Immunology, Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6199-3016","authenticated-orcid":false,"given":"Fritz","family":"Diekmann","sequence":"additional","affiliation":[{"name":"Hospital Cl\u00ednic Barcelona, Nephrology and Kidney Transplantation, Barcelona, Spain,"},{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Barcelona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6320-9133","authenticated-orcid":false,"given":"Mirjam H.M.","family":"Heemskerk","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center, Department of Hematology, Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8737-5005","authenticated-orcid":false,"given":"Jordi","family":"Rovira","sequence":"additional","affiliation":[{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Barcelona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6700-188X","authenticated-orcid":false,"given":"Sebastiaan","family":"Heidt","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center, Department of Immunology, Leiden, Netherlands."},{"name":"Erasmus Medical Center, Department of Internal Medicine, Rotterdam, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,9,3]]},"container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.0000001244","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:00:26Z","timestamp":1788454826000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.0000001244"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1681\/asn.0000001244","relation":{},"ISSN":["1046-6673","1533-3450"],"issn-type":[{"value":"1046-6673","type":"print"},{"value":"1533-3450","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]},"assertion":[{"value":"2026-03-13","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-28","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}