{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T20:30:39Z","timestamp":1793392239782,"version":"4.5.0"},"reference-count":41,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T00:00:00Z","timestamp":1676592000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["19ck0106288"],"award-info":[{"award-number":["19ck0106288"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2023,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The efficacy of immune checkpoint inhibitors is limited in refractory solid tumors. T\u2010cell receptor gene\u2010modified T (TCR\u2010T)\u2010cell therapy has attracted attention as a new immunotherapy for refractory cold tumors. We first investigated the preclinical efficacy and mode of action of TCR\u2010T cells combined with the pullulan nanogel:long peptide antigen (LPA) vaccine in a mouse sarcoma model that is resistant to immune checkpoint inhibition. Without lymphodepletion, the pullulan nanogel:LPA vaccine markedly increased the number of TCR\u2010T cells in the draining lymph node and tumor tissue. This change was associated with enhanced CXCR3 expression in TCR\u2010T cells in the draining lymph node. In the phase 1 trial, autologous New York esophageal squamous cell carcinoma 1 (NY\u2010ESO\u20101)\u2010specific TCR\u2010T cells were infused twice into HLA\u2010matched patients with NY\u2010ESO\u20101<jats:sup>+<\/jats:sup> soft tissue sarcoma (STS). The pullulan nanogel:LPA vaccine contains an epitope recognized by TCR\u2010T cells, and it was subcutaneously injected 1 day before and 7\u2009days after the infusion of TCR\u2010T cells. Lymphodepletion was not performed. Three patients with refractory synovial sarcoma (SS) were treated. Two out of the three patients developed cytokine release syndrome (CRS) with low\u2010to\u2010moderate cytokine level elevation. We found obvious tumor shrinkage lasting for more than 2\u2009years by tumor imaging and long\u2010term persistence of TCR\u2010T cells in one patient. In conclusion, NY\u2010ESO\u20101\u2010specific TCR\u2010T\u2010cell therapy plus vaccination with the pullulan nanogel carrying an LPA containing the NY\u2010ESO\u20101 epitope without lymphodepletion is feasible and can induce promising long\u2010lasting therapeutic effects in refractory SS (Registration ID: JMA\u2010IIA00346).<\/jats:p>","DOI":"10.1002\/ijc.34453","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T10:11:09Z","timestamp":1675332669000},"page":"2554-2566","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["A phase 1 trial of <scp>NY\u2010ESO<\/scp>\u20101\u2010specific <scp>TCR<\/scp>\u2010engineered T\u2010cell therapy combined with a lymph node\u2010targeting nanoparticulate peptide vaccine for the treatment of advanced soft tissue sarcoma"],"prefix":"10.1002","volume":"152","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7581-2615","authenticated-orcid":false,"given":"Mikiya","family":"Ishihara","sequence":"first","affiliation":[{"name":"Cancer Center Mie University Hospital  Tsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7511-6388","authenticated-orcid":false,"given":"Yoshihiro","family":"Nishida","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Nagoya University Hospital  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigehisa","family":"Kitano","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical Development The Cancer Institute Hospital of Japanese Foundation for Cancer Research  Tokyo Japan"},{"name":"Department of Experimental Therapeutics National Cancer Center Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Kawai","sequence":"additional","affiliation":[{"name":"Musculoskeletal Oncology and Rehabilitation National Cancer Center Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Muraoka","sequence":"additional","affiliation":[{"name":"Division of Translational Oncoimmunology Aichi Cancer Center Research Institute  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumiyasu","family":"Momose","sequence":"additional","affiliation":[{"name":"Department of Personalized Cancer Immunotherapy Mie University Graduate School of Medicine  Tsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naozumi","family":"Harada","sequence":"additional","affiliation":[{"name":"United Immunity, Co., Ltd.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Miyahara","sequence":"additional","affiliation":[{"name":"Department of Personalized Cancer Immunotherapy Mie University Graduate School of Medicine  Tsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naohiro","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Personalized Cancer Immunotherapy Mie University Graduate School of Medicine  Tsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyoshi","family":"Hattori","sequence":"additional","affiliation":[{"name":"Laboratory of Advanced Therapy, Clinical Research Center National Hospital Organization Nagoya Medical Center  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohichi","family":"Takada","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Sapporo Medical University School of Medicine  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Emori","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Sapporo Medical University School of Medicine  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeki","family":"Kakunaga","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Osaka National Hospital  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Endo","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuro","family":"Sasada","sequence":"additional","affiliation":[{"name":"Department of Cancer Immunotherapy Kanagawa Cancer Center Research Institute  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiichi","family":"Sato","sequence":"additional","affiliation":[{"name":"Institute of Medical Science Tokyo Medical University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomomi","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Medical Innovation Osaka University Hospital  Suita Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Matsumine","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Rehabilitation Medicine, Unit of Surgery, Division of Medicine, Faculty of Medical Sciences University of Fukui  Yoshida\u2010gun Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Nagata","sequence":"additional","affiliation":[{"name":"Department of Community Medicine Nagasaki University Graduate School of Biomedical Sciences  Nagasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Personalized Cancer Immunotherapy Mie University Graduate School of Medicine  Tsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichi","family":"Kageyama","sequence":"additional","affiliation":[{"name":"Department of Immuno\u2010Gene therapy Mie University Graduate School of Medicine  Tsu Japan"},{"name":"Department of Medical Oncology\/Chemotherapy Center Suzuka Kaisei Hospital  Suzuka 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  Tsu Japan"},{"name":"Department of Immuno\u2010Gene therapy Mie University Graduate School of Medicine  Tsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,2,17]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.01.016"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-08-802926"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aav8692"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay5967"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/ma00064a011"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/ma960786e"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.2174\/157016311798109371"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/nn502975r"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI97642"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2009.09.018"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-11-246"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.12.6375"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903649"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2013.02.056"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-003811"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-05-552729"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.1282"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-020-02483-1"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.suronc.2018.07.012"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)00026-1"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30726"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.13769"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.27313"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.8.1105"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.5.2591"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215175"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050732"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30864-7"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2019.08.003"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.10.478"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-06-793141"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2020.06.025"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-021-02892-w"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-0526"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32491-x"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2014.32.15_suppl.e22121"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30074-8"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-17-1417"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10147-017-1199-6"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.01763"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.34453","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ijc.34453","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.34453","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T08:24:20Z","timestamp":1692692660000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.34453"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,17]]},"references-count":41,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2023,6,15]]}},"alternative-id":["10.1002\/ijc.34453"],"URL":"https:\/\/doi.org\/10.1002\/ijc.34453","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,17]]},"assertion":[{"value":"2022-09-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}