{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T06:02:54Z","timestamp":1790056974870,"version":"4.0.1"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":226,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100020643","name":"MRC","doi-asserted-by":"publisher","award":["MR\/W006308\/1"],"award-info":[{"award-number":["MR\/W006308\/1"]}],"id":[{"id":"10.13039\/501100020643","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["338308\/Z\/25\/Z"],"award-info":[{"award-number":["338308\/Z\/25\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Dynamic Molecular Cell Biology"},{"DOI":"10.13039\/100031787","name":"Immunocore","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100031787","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011821","name":"Ministry of Education of Saudi Arabia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011821","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Synthetic T cell receptor (TCR) engagers are cancer therapeutics that activate T cells through recognition of antigens on the tumor cell surface. Immune-mobilizing monoclonal TCRs against cancer (ImmTAC) are composed of the extracellular domains of the alpha and beta chains of an affinity-enhanced TCR recognizing a tumor-associated antigenic peptide-major histocompatibility complex (MHC) complex linked to an scFv fragment of an antibody against CD3\u03b5. A first-in-class ImmTAC, Tebentafusp, is approved for the treatment of metastatic uveal melanoma. Here we asked how ImmTACs activate human primary cytotoxic T lymphocytes (CTL) in response to antigen-presenting tumor target cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>We used a recently established experimental strategy to generate active and matched suppressed CTL in vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>ImmTACs could elicit tumor cell cytolysis in response to endogenous antigen presentation by both active and suppressed CTL, but much less so for IFN\u03b3 secretion, in a manner dependent on the engager affinity for CD3\u03b5. ImmTACs did so by enhancing the efficient execution of subcellular CTL polarization steps required for effective cytolysis and could trigger calcium signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These data establish that ImmTACs are powerful inducers of CTL cytotoxicity and do so with a comparable efficacy and mechanism as direct engagement of a TCR by peptide-MHC. ImmTACs retain this capability under suppressive conditions comparable to those in the tumor microenvironment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/immadv\/ltag020","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T06:42:02Z","timestamp":1786689722000},"source":"Crossref","is-referenced-by-count":0,"title":["ImmTACs overcome cytotoxic T cell suppression"],"prefix":"10.1093","volume":"6","author":[{"given":"Lan","family":"Huynh","sequence":"first","affiliation":[{"name":"School of Cellular and Molecular Medicine, University of Bristol , Bristol ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Aljohani","sequence":"additional","affiliation":[{"name":"School of Cellular and Molecular Medicine, University of Bristol , Bristol ,","place":["United 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