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Currently, patients with small cell lung cancer face a significant dearth of effective alternative treatment options once they experience recurrence and progression after first\u2010line therapy. Despite the promising efficacy of immunotherapy, particularly immune checkpoint inhibitors in non\u2010small cell lung cancer (NSCLC) and various other tumours, its impact on significantly enhancing the prognosis of SCLC patients remains elusive. DLL3 has emerged as a compelling target for targeted therapy in SCLC due to its high expression on the membranes of SCLC and other neuroendocrine carcinoma cells, with minimal to no expression in normal cells. Our previous work led to the development of a novel multiple chain chimeric antigen receptor (CAR) leveraging the TREM1 receptor and DAP12, which efficiently activated T cells and conferred potent cell cytotoxicity. In this study, we have developed a DLL3\u2010TREM1\/DAP12 CAR\u2010T (DLL3\u2010DT CAR\u2010T) therapy, demonstrating comparable anti\u2010tumour efficacy against SCLC cells in vitro. In murine xenograft and patient\u2010derived xenograft models, DLL3\u2010DT CAR\u2010T cells exhibited a more robust tumour eradication efficiency than second\u2010generation DLL3\u2010BBZ CAR\u2010T cells. Furthermore, we observed elevated memory phenotypes, induced durable responses, and activation under antigen\u2010presenting cells in DLL3\u2010DT CAR\u2010T cells. Collectively, these findings suggest that DLL3\u2010DT CAR\u2010T cells may offer a novel and potentially effective therapeutic strategy for treating DLL3\u2010expressing SCLC and other solid tumours.<\/jats:p>","DOI":"10.1111\/imm.13776","type":"journal-article","created":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T04:35:57Z","timestamp":1710218157000},"page":"362-374","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["<scp>TREM1<\/scp>\n                    \/\n                    <scp>DAP12<\/scp>\n                    based novel multiple chain\n                    <scp>CAR\u2010T<\/scp>\n                    cells targeting\n                    <scp>DLL3<\/scp>\n                    show robust anti\u2010tumour efficacy for small cell lung cancer"],"prefix":"10.1111","volume":"172","author":[{"given":"Fengqi","family":"Nie","sequence":"first","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Nanjing Medical University  Nanjing China"},{"name":"Department of Oncology The Second Affiliated Hospital, Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuli","family":"Chen","sequence":"additional","affiliation":[{"name":"Suzhou Cancer Center Core Laboratory, Suzhou Municipal Hospital, Gusu School The Affiliated Suzhou Hospital of Nanjing Medical University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanming","family":"Hu","sequence":"additional","affiliation":[{"name":"Suzhou Cancer Center Core Laboratory, Suzhou Municipal Hospital, Gusu School The Affiliated Suzhou Hospital of Nanjing Medical University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Huang","sequence":"additional","affiliation":[{"name":"Suzhou Cancer Center Core Laboratory, Suzhou Municipal Hospital, Gusu School The Affiliated Suzhou Hospital of Nanjing Medical University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefei","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Huzhou Central Hospital, Affiliated Central Hospital, Huzhou University  Huzhou Zhejiang China"},{"name":"Huzhou Key Laboratory of Precision Diagnosis and Treatment in Respiratory Diseases Huzhou Central Hospital  Huzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingsheng","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Peking University People's Hospital  Beijing China"},{"name":"Thoracic Oncology Institute, Peking University People's Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0419-9139","authenticated-orcid":false,"given":"Mantang","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Peking University People's Hospital  Beijing China"},{"name":"Thoracic Oncology Institute, Peking University People's Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enxiu","family":"Wang","sequence":"additional","affiliation":[{"name":"Nanjing CART Medical Technology Co., Ltd.  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