{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:50:48Z","timestamp":1791276648874,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004257","name":"Helse Vest","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004257","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"abstract":"<jats:p>\n                    Ovarian cancer (OC) is typically associated with poor prognosis and high mortality. Chimeric antigen receptor (CAR) T\u2010cell therapy offers a promising strategy, yet its application in solid tumours remains constrained by limited efficacy and on\u2010target\/off\u2010tumour toxicities. We previously developed K101CAR T\u00a0cells targeting CA125, the cleaved extracellular domain of MUC16, and demonstrated potent antitumour activity against OC. However, because MUC16 exhibits low\u2010level expression in certain normal tissues, safety concerns remain regarding potential off\u2010tumour effects. We designed a combinatorial CAR composed of two single\u2010chain variable fragments (scFvs): (i) TAG\u201072 targeting the Sialyl\u2010Tn antigen highly expressed on malignant cells, and (ii) the K101 scFv. The first unit is linked to a CD3\u03b6 signalling domain, whereas the second is linked to a 4\u20101BB costimulatory domain, leading to a combinatorial CAR fully reactive against double\u2010positive targets, Tz\u2010KBBCAR. We demonstrate that Tz\u2010KBBCAR T\u00a0cells efficiently eliminate MUC16\n                    <jats:sup>+<\/jats:sup>\n                    \/TAG\u201072\n                    <jats:sup>+<\/jats:sup>\n                    \u2010, while sparing MUC16\n                    <jats:sup>+<\/jats:sup>\n                    \/TAG\u201072\n                    <jats:sup>\u2212<\/jats:sup>\n                    \u2010 cells\n                    <jats:italic>in vitro<\/jats:italic>\n                    and markedly suppress tumour progression\n                    <jats:italic>in vivo<\/jats:italic>\n                    . We also observed that compared to K101CAR T\u00a0cells, Tz\u2010KBBCAR T\u00a0cells exhibit enhanced expansion, sustained viability, and a reduced exhaustion phenotype. Overall, our study presents an efficient combinatorial CAR T\u2010cell strategy predicted to be safer than single CAR T\u2010cell therapy for OC.\n                  <\/jats:p>","DOI":"10.1111\/febs.70760","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:55:56Z","timestamp":1791273356000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Combining\n                    <scp>TAG<\/scp>\n                    \u2010\n                    <scp>72CAR<\/scp>\n                    with anti\u2010\n                    <scp>MUC16CAR<\/scp>\n                    improves the potency of ovarian cancer treatment"],"prefix":"10.1111","author":[{"given":"Alicia","family":"Villatoro","sequence":"first","affiliation":[{"name":"Translational Research Unit, Section for Cellular Therapy, Department of Oncology Oslo University Hospital  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Santiago de Compostela (SERGAS)  Spain"},{"name":"Department of Medicine Universidad de Santiago de Compostela (USC)  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Gelebart","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, Precision Oncology Research Group University of Bergen  Norway"},{"name":"Centre for Cancer Biomarkers (CCBIO) University of Bergen  Norway"},{"name":"Hematology section Haukeland University Hospital  Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmet","family":"McCormack","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, Precision Oncology Research Group University of Bergen  Norway"},{"name":"Centre for Cancer Biomarkers (CCBIO) University of Bergen  Norway"},{"name":"Hematology section Haukeland University Hospital  Bergen 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