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TCR-like T cells, capable of recognizing intracellular antigen\u2013derived 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\u2013restricted LMP2\n                    <jats:sub>426<\/jats:sub>\n                    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-\u03b3 secretion, even when engaging with target cells that naturally present antigens. Moreover, a costimulatory signal\u2013armed 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\/LMP2\n                    <jats:sub>426<\/jats:sub>\n                    for the treatment of EBV-LPDs, providing a potential therapeutic solution for targeting of intracellular antigens in cancer immunotherapy.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.178572","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T14:00:37Z","timestamp":1747836037000},"source":"Crossref","is-referenced-by-count":9,"title":["Targeting intracellular LMP2 with costimulatory signal\u2013armed antibody-like TCR T cells"],"prefix":"10.1172","volume":"10","author":[{"given":"Jiali","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Hematology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China."},{"name":"Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, 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