{"title":"用共刺激信号武装抗体样TCR T细胞靶向细胞内LMP2。","authors":"Jiali Cheng, Xuelian Hu, Zhenyu Dai, Yuhao Zeng, Jin Jin, Wei Mu, Qiaoe Wei, Xiangyin Jia, Jianwei Liu, Meng Xie, Qian Luo, Guang Hu, Gaoxiang Wang, Xiaojian Zhu, Jianfeng Zhou, Min Xiao, Jue Wang, Taochao Tan, Liang Huang","doi":"10.1172/jci.insight.178572","DOIUrl":null,"url":null,"abstract":"<p><p>Expanding the repertoire of CAR therapies to include intracellular antigens holds promise for treating a broad spectrum of malignancies. TCR-like T cells, capable of recognizing intracellular antigen-derived peptides in complex with HLA molecules (pHLA), represent a promising strategy in the field of engineered cellular therapy. This study introduced antibody-like TCR (abTCR) T cells that specifically targeted HLA-A*02:01-restricted LMP2426 peptides, a typical Epstein-Barr virus (EBV) latency II protein, for the treatment of EBV-associated lymphoproliferative diseases (EBV-LPDs). Compared with classic CAR T cells targeting the same epitope, abTCR T cells demonstrated superior efficiency, including increased CD107A expression, enhanced cytotoxicity, and elevated IFN-γ secretion, even when engaging with target cells that naturally present antigens. Moreover, a costimulatory signal-armed abTCR (Co-abTCR), which integrated a costimulatory structure with the abTCR, further enhanced the proliferation and in vivo tumoricidal efficacy of transfected T cells. Collectively, our study developed a potentially novel TCR-like T cell therapy that targets HLA-A*02/LMP2426 for the treatment of EBV-LPDs, providing a potential therapeutic solution for targeting of intracellular antigens in cancer immunotherapy.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":"10 10","pages":""},"PeriodicalIF":6.3000,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Targeting intracellular LMP2 with costimulatory signal-armed antibody-like TCR T cells.\",\"authors\":\"Jiali Cheng, Xuelian Hu, Zhenyu Dai, Yuhao Zeng, Jin Jin, Wei Mu, Qiaoe Wei, Xiangyin Jia, Jianwei Liu, Meng Xie, Qian Luo, Guang Hu, Gaoxiang Wang, Xiaojian Zhu, Jianfeng Zhou, Min Xiao, Jue Wang, Taochao Tan, Liang Huang\",\"doi\":\"10.1172/jci.insight.178572\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Expanding the repertoire of CAR therapies to include intracellular antigens holds promise for treating a broad spectrum of malignancies. TCR-like T cells, capable of recognizing intracellular antigen-derived peptides in complex with HLA molecules (pHLA), represent a promising strategy in the field of engineered cellular therapy. This study introduced antibody-like TCR (abTCR) T cells that specifically targeted HLA-A*02:01-restricted LMP2426 peptides, a typical Epstein-Barr virus (EBV) latency II protein, for the treatment of EBV-associated lymphoproliferative diseases (EBV-LPDs). Compared with classic CAR T cells targeting the same epitope, abTCR T cells demonstrated superior efficiency, including increased CD107A expression, enhanced cytotoxicity, and elevated IFN-γ secretion, even when engaging with target cells that naturally present antigens. Moreover, a costimulatory signal-armed abTCR (Co-abTCR), which integrated a costimulatory structure with the abTCR, further enhanced the proliferation and in vivo tumoricidal efficacy of transfected T cells. Collectively, our study developed a potentially novel TCR-like T cell therapy that targets HLA-A*02/LMP2426 for the treatment of EBV-LPDs, providing a potential therapeutic solution for targeting of intracellular antigens in cancer immunotherapy.</p>\",\"PeriodicalId\":14722,\"journal\":{\"name\":\"JCI insight\",\"volume\":\"10 10\",\"pages\":\"\"},\"PeriodicalIF\":6.3000,\"publicationDate\":\"2025-05-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JCI insight\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1172/jci.insight.178572\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JCI insight","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1172/jci.insight.178572","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Targeting intracellular LMP2 with costimulatory signal-armed antibody-like TCR T cells.
Expanding the repertoire of CAR therapies to include intracellular antigens holds promise for treating a broad spectrum of malignancies. TCR-like T cells, capable of recognizing intracellular antigen-derived peptides in complex with HLA molecules (pHLA), represent a promising strategy in the field of engineered cellular therapy. This study introduced antibody-like TCR (abTCR) T cells that specifically targeted HLA-A*02:01-restricted LMP2426 peptides, a typical Epstein-Barr virus (EBV) latency II protein, for the treatment of EBV-associated lymphoproliferative diseases (EBV-LPDs). Compared with classic CAR T cells targeting the same epitope, abTCR T cells demonstrated superior efficiency, including increased CD107A expression, enhanced cytotoxicity, and elevated IFN-γ secretion, even when engaging with target cells that naturally present antigens. Moreover, a costimulatory signal-armed abTCR (Co-abTCR), which integrated a costimulatory structure with the abTCR, further enhanced the proliferation and in vivo tumoricidal efficacy of transfected T cells. Collectively, our study developed a potentially novel TCR-like T cell therapy that targets HLA-A*02/LMP2426 for the treatment of EBV-LPDs, providing a potential therapeutic solution for targeting of intracellular antigens in cancer immunotherapy.
期刊介绍:
JCI Insight is a Gold Open Access journal with a 2022 Impact Factor of 8.0. It publishes high-quality studies in various biomedical specialties, such as autoimmunity, gastroenterology, immunology, metabolism, nephrology, neuroscience, oncology, pulmonology, and vascular biology. The journal focuses on clinically relevant basic and translational research that contributes to the understanding of disease biology and treatment. JCI Insight is self-published by the American Society for Clinical Investigation (ASCI), a nonprofit honor organization of physician-scientists founded in 1908, and it helps fulfill the ASCI's mission to advance medical science through the publication of clinically relevant research reports.