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Here, we report pre\u2010clinical and phase I clinical trial data (NCT03953599) of this T\u2010cell therapy for refractory and relapsed (R\/R) B\u2010cell acute lymphoblastic leukemia (B\u2010ALL) patients. STAR consists of two protein modules each containing an antibody light or heavy chain variable region and TCR \u03b1 or \u03b2 chain constant region fused to the co\u2010stimulatory domain of OX40. T\u2010cells were transduced with a STAR\u2010OX40 lentiviral vector. A leukemia xenograft mouse model was used to assess the STAR\/STAR\u2010OX40 T cell antitumor activity. Eighteen patients with R\/R B\u2010ALL were enrolled into the clinical trial. In a xenograft mouse model, STAR\u2010T\u2010cells exhibited superior tumor\u2010specific cytotoxicity compared with conventional CAR\u2010T cells. Incorporating OX40 into STAR further improved the proliferation and persistence of tumor\u2010targeting T\u2010cells. In our clinical trial, 100% of patients achieved complete remission 4\u2009weeks post\u2010STAR\u2010OX40 T\u2010cell infusion and 16\/18 (88.9%) patients pursued consolidative allogeneic hematopoietic stem cell transplantation (allo\u2010HSCT). Twelve of 16 patients (75%) remained leukemia\u2010free after a median follow\u2010up of 545 (433\u2013665) days. The two patients without consolidative allo\u2010HSCT relapsed on Day 58 and Day 186. Mild cytokine release syndrome occurred in 10\/18 (55.6%) patients, and 2 patients experienced grade III neurotoxicity. Our preclinical studies demonstrate super anti\u2010tumor potency of STAR\u2010OX40 T\u2010cells compared with conventional CAR\u2010T cells. The first\u2010in\u2010human clinical trial shows that STAR\u2010OX40 T\u2010cells are tolerable and an effective therapeutic platform for treating R\/R B\u2010ALL.<\/jats:p>","DOI":"10.1002\/ajh.26586","type":"journal-article","created":{"date-parts":[[2022,5,2]],"date-time":"2022-05-02T05:49:05Z","timestamp":1651470545000},"page":"992-1004","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["A novel adoptive synthetic <scp>TCR<\/scp> and antigen receptor (<scp>STAR<\/scp>) <scp>T\u2010Cell<\/scp> therapy for <scp>B\u2010Cell<\/scp> acute lymphoblastic leukemia"],"prefix":"10.1002","volume":"97","author":[{"given":"Jiasheng","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Basic Medical Sciences Tsinghua University School of Medicine  Beijing China"},{"name":"Tsinghua\u2010Peking Center for Life Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hebei Yanda Lu Daopei Hospital  Langfang China"},{"name":"Lu Daopei Institute of Hematology  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixiao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences Tsinghua University School of Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences Tsinghua University School of Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences Tsinghua University School of Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lemei","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences Tsinghua University School of Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junfang","family":"Yang","sequence":"additional","affiliation":[{"name":"Hebei Yanda Lu Daopei Hospital  Langfang China"},{"name":"Lu Daopei Institute of Hematology  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Li","sequence":"additional","affiliation":[{"name":"Hebei Yanda Lu Daopei Hospital  Langfang China"},{"name":"Lu Daopei Institute of Hematology  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanyang","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences Tsinghua University School of Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzhong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences Tsinghua University School of Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangna","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences Tsinghua University School of Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Rui","sequence":"additional","affiliation":[{"name":"China Immunotech Biotechnology Co. 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