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Chimeric antigen receptor (CAR) T-cell therapy targeting BCMA has shown efficacy in relapsed or refractory MM, but it faces resistance due to antigen loss and the tumor microenvironment. Bispecific T-cell engaging (BITE) antibodies also encounter clinical challenges, including short half-lives requiring continuous infusion and potential toxicities.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>To address these issues, we developed a lentiviral system to engineer T cells that secrete \u03b1B7-H3-\u03b1CD3 bispecific engager molecules (\u03b1B7-H3-\u03b1CD3 ENG-T cells). We evaluated their effectiveness against MM cells with varying B7-H3 expression levels, from B7-H3<jats:sup>neg<\/jats:sup> to B7-H3<jats:sup>high<\/jats:sup>.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The \u03b1B7-H3-\u03b1CD3 ENG-T cells demonstrated significant anti-tumor activity against MM cell lines expressing B7-H3. SupT-1 cells (B7-H3<jats:sup>neg<\/jats:sup>) served as controls and exhibited minimal cytotoxicity from \u03b1B7-H3-\u03b1CD3 ENG T cells. In contrast, these engineered T cells showed dose-dependent killing of B7-H3-expressing MM cells: NCI-H929 (B7-H3<jats:sup>low<\/jats:sup>), L-363 (B7-H3<jats:sup>medium<\/jats:sup>), and KMS-12-PE (B7-H3<jats:sup>high<\/jats:sup>). For NCI-H929 cells, cytotoxicity reached 38.5\u2009\u00b1\u20097.4% (<jats:italic>p<\/jats:italic>\u2009=\u20090.0212) and 54.0\u2009\u00b1\u20099.2% (<jats:italic>p<\/jats:italic>\u2009=\u20090.0317) at effector-to-target (E:T) ratios of 5:1 and 10:1, respectively. Against L-363 cells, cytotoxicity was 56.6\u2009\u00b1\u20093.2% (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) and 71.4\u2009\u00b1\u20095.2% (<jats:italic>p<\/jats:italic>\u2009=\u20090.0002) at E:T ratios of 5:1 and 10:1, respectively. For KMS-12-PE cells, significant cytotoxic effects were observed even at an E:T ratio of 1:1, with 27.2\u2009\u00b1\u20093.7% (<jats:italic>p<\/jats:italic>\u2009=\u20090.0004), 44.4\u2009\u00b1\u20093.7% (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), and 68.6\u2009\u00b1\u20099.2% (<jats:italic>p<\/jats:italic>\u2009=\u20090.0004) cytotoxicity at E:T ratios of 1:1, 5:1, and 10:1, respectively.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>These results indicate that \u03b1B7-H3-\u03b1CD3 ENG T cells could be a promising therapy for B7-H3-positive MM. They may enhance current MM treatments and improve overall outcomes. Additional preclinical and clinical research is required to fully assess their therapeutic potential.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12967-024-05923-z","type":"journal-article","created":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T10:32:23Z","timestamp":1736764343000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Engineered T cells secreting \u03b1B7-H3-\u03b1CD3 bispecific engagers for enhanced anti-tumor activity against B7-H3 positive multiple myeloma: a novel therapeutic approach"],"prefix":"10.1186","volume":"23","author":[{"given":"Punchita","family":"Rujirachaivej","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teerapong","family":"Siriboonpiputtana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kornkan","family":"Choomee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamonlapat","family":"Supimon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanich","family":"Sangsuwannukul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pucharee","family":"Songprakhon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krissada","family":"Natungnuy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piriya","family":"Luangwattananun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pornpimon","family":"Yuti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8347-3000","authenticated-orcid":false,"given":"Mutita","family":"Junking","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pa-thai","family":"Yenchitsomanus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,13]]},"reference":[{"key":"5923_CR1","doi-asserted-by":"publisher","first-page":"17046","DOI":"10.1038\/nrdp.2017.46","volume":"3","author":"SK Kumar","year":"2017","unstructured":"Kumar SK, Rajkumar V, Kyle RA, et al. 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