{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:20:27Z","timestamp":1790742027884,"version":"4.1.0"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T00:00:00Z","timestamp":1734998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007835","name":"Wenzhou Medical University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007835","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Challenges remain in reducing antigen escape and tumor recurrence while CAR-T cell therapy has substantially improved outcomes in the treatment of multiple myeloma. T cell receptor fusion construct (TRuC)-T cells, which utilize intact T cell receptor (TCR)-CD3 complex to eliminate tumor cells in a non-major histocompatibility complex (MHC)-restricted manner, represent a promising strategy. Moreover, interleukin-7 (IL-7) is known to enhance the proliferation and survival of T cells. C-C motif chemokine ligand 21 (CCL21) is a ligand for chemokine C-C motif receptor 7 (CCR7) and exhibits strong chemotaxis against na\u00efve T cells and antigen-presenting cells such as dendritic cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The bispecific TRuC-T cells simultaneously targeting B cell maturation antigen (BCMA) and CD2 subset 1 (CS1) were constructed by pairing two of five subunits (i.e., TCR\u03b1C, TCR\u03b2C, CD3\u03b3, CD3\u03b4, and CD3\u03f5) in the TCR\/CD3 complex and were named C-AC-B-3E, C-BC-B-3E, C-3G-B-3E, C-3D-B-3E, C-3E-B-3E, B-3E-C-3E, B-3G-C-3E, and B-3D-C-3E. Additionally, the BCMA\/CS1 bispecific TRuC-T cells secreting IL-7 and CCL21, named BC-7\u00d721 TRuC-T cells, were generated. All of the bispecific TRuC-T cells were characterized and tested\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Following the optimization of various pairs of two subunits of TCR\/CD3 complex, B-3G-C-3E TRuC-T cells, characterized by incorporating CD3\u03b3 and CD3\u03b5, exhibited the strongest myeloma-specific cytotoxicity. Furthermore, the bispecific BC-7\u00d721 TRuC-T cells had stronger proliferation, chemotaxis, and cytotoxicity\n                      <jats:italic>in vitro<\/jats:italic>\n                      . Accordingly, the bispecific BC-7\u00d721 TRuC-T cells showed better persistence in vivo so as to effectively suppress tumor growth in the NCG mouse xenograft model of MM.1S multiple myeloma.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This study demonstrated that BC-7\u00d721 TRuC-T cells, engineered through the optimization of the two subunits of TCR\/CD3 complex and a co-expression cytokine strategy, may offer a novel and effective therapy for relapsed\/refractory multiple myeloma.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2024.1502936","type":"journal-article","created":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T01:37:24Z","timestamp":1735004244000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Optimized BCMA\/CS1 bispecific TRuC-T cells 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