{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T06:32:14Z","timestamp":1781850734662,"version":"3.54.5"},"reference-count":39,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T00:00:00Z","timestamp":1694044800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["21cm0106351h0003"],"award-info":[{"award-number":["21cm0106351h0003"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21H02990"],"award-info":[{"award-number":["21H02990"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Adoptive immunotherapy using genetically engineered patient\u2010derived lymphocytes to express tumor\u2010reactive receptors is a promising treatment for malignancy. However, utilization of autologous T cells in this therapy limits the quality of gene\u2010engineered T cells, thereby inhibiting the timely infusion of the cells into patients. In this study, we evaluated the anti\u2010tumor efficacy and the potential to induce graft\u2010versus\u2010host disease (GVHD) in T cell receptor (TCR) gene\u2010engineered allogeneic T cells that downregulate the endogenous TCR and HLA class I molecules with the aim of developing an \u201coff\u2010the\u2010shelf\u201d cell product with expanded application of genetically engineered T cells. We transduced human lymphocytes with a high\u2010affinity TCR specific to the cancer\/testis antigen NY\u2010ESO\u20101 using a novel retrovirus vector with siRNAs specific to the endogenous TCR (siTCR vector). These T cells showed reduced expression of endogenous TCR and minimized reactivity to allogeneic cells in vitro. In non\u2010obese diabetic\/SCID\/\u03b3c<jats:sup>null<\/jats:sup> mice, TCR gene\u2010transduced T cells induced tumor regression without development of GVHD. A lentivirus\u2010based CRISPR\/Cas9 system targeting \u03b2\u20102 microglobulin in TCR gene\u2010modified T cells silenced the HLA class I expression and prevented allogeneic CD8<jats:sup>+<\/jats:sup> T cell stimulation without disrupting their anti\u2010tumor capacity. This report is the first demonstration that siTCR technology is effective in preventing GVHD. Adoptive cell therapy with allogeneic T cells engineered with siTCR vector may be useful in developing an \u201coff\u2010the\u2010shelf\u201d therapy for patients with malignancy.<\/jats:p>","DOI":"10.1111\/cas.15954","type":"journal-article","created":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T08:41:00Z","timestamp":1694076060000},"page":"4172-4183","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["T cell receptor gene\u2010modified allogeneic T cells with siRNA for endogenous T cell receptor induce efficient tumor regression without graft\u2010versus\u2010host disease"],"prefix":"10.1111","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9962-366X","authenticated-orcid":false,"given":"Satomi","family":"Okada","sequence":"first","affiliation":[{"name":"Department of Oncology Nagasaki University Graduate School of Biomedical Sciences  Nagasaki Japan"},{"name":"Department of Surgery Nagasaki University Graduate School of Biomedical Sciences  Nagasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4493-7052","authenticated-orcid":false,"given":"Daisuke","family":"Muraoka","sequence":"additional","affiliation":[{"name":"Department of Oncology Nagasaki University Graduate School of Biomedical Sciences  Nagasaki Japan"},{"name":"Division of Translational Oncoimmunology Aichi Cancer Center Research Institute  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi","family":"Yasui","sequence":"additional","affiliation":[{"name":"Department of Oncology Nagasaki University Graduate School of Biomedical Sciences  Nagasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isao","family":"Tawara","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Mie University Graduate School of Medicine  Mie Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayumi","family":"Kawamura","sequence":"additional","affiliation":[{"name":"Takara Bio Inc.  Shiga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachiko","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Takara Bio Inc.  Shiga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junichi","family":"Mineno","sequence":"additional","affiliation":[{"name":"Takara Bio Inc.  Shiga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8556-2437","authenticated-orcid":false,"given":"Naohiro","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Personalized Cancer Immunotherapy Mie University Graduate School of Medicine  Mie Japan"},{"name":"Department of Bioengineering, School of Engineering The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Shiku","sequence":"additional","affiliation":[{"name":"Department of Personalized Cancer Immunotherapy Mie University Graduate School of Medicine  Mie Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susumu","family":"Eguchi","sequence":"additional","affiliation":[{"name":"Department of Surgery Nagasaki University Graduate School of Biomedical Sciences  Nagasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8012-4796","authenticated-orcid":false,"given":"Hiroaki","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Department of Oncology Nagasaki University Graduate School of Biomedical Sciences  Nagasaki Japan"},{"name":"Leading Medical Research Core Unit Nagasaki University Graduate School of Biomedical Sciences  Nagasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,9,7]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa8172"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2015.03.001"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3239"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1606774"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504030"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1712126"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32591-7"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1809064"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1915745"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1129003"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-03-211714"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxw022"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-1280"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.32.2537"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/CJI.0b013e3182829903"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-1559"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3910"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-1450"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/mtna.2012.52"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-02-337089"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000173"},{"issue":"6","key":"e_1_2_11_23_1","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2021-003811","article-title":"NY\u2010ESO\u20101\u2013specific 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