{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:05:27Z","timestamp":1790859927738,"version":"4.1.0"},"reference-count":55,"publisher":"BMJ","issue":"11","license":[{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"unspecified","delay-in-days":17,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001021","name":"Damon Runyon Cancer Research Foundation","doi-asserted-by":"publisher","award":["DRG-2529-24"],"award-info":[{"award-number":["DRG-2529-24"]}],"id":[{"id":"10.13039\/100001021","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005410","name":"American-Italian Cancer Foundation","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100005410","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100023479","name":"CRIS Cancer Foundation","doi-asserted-by":"publisher","award":["outback2021_6"],"award-info":[{"award-number":["outback2021_6"]}],"id":[{"id":"10.13039\/501100023479","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["CA238268"],"award-info":[{"award-number":["CA238268"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["K99CA303346"],"award-info":[{"award-number":["K99CA303346"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2025,10,23]]},"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chimeric antigen receptor (CAR)-T cell therapy has achieved significant success in hematologic malignancies; however, its efficacy in solid tumors remains limited. A major limitation is the difficulty in identifying suitable target antigens that are abundantly expressed on the surface of tumor cells while sparing life-sustaining normal tissues.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We identified MUC17, a membrane-tethered mucin-type glycoprotein with minimal expression in normal tissues and frequent upregulation in gastric cancers, as a potential target for CAR-T therapy. We developed and validated MUC17-specific CAR-T cells incorporating a 4-1BB\/CD3\u03b6 signaling domain. In vitro assays assessed cytotoxicity, cytokine secretion, and T cell phenotypes across multiple gastric cancer cell lines, including CRISPR-mediated MUC17 knockout controls. In vivo efficacy was evaluated using NSG xenograft models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MUC17 CAR-T cells exhibited potent, antigen-specific cytotoxicity, robust cytokine release, and sustained effector functions characterized by enrichment of central memory phenotypes. In vivo, MUC17 CAR-T cells significantly suppressed tumor growth without signs of toxicity in GSU and ASPC-1 models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings support MUC17 as a promising immunotherapeutic target for gastric cancer and demonstrate how targeting glycocalyx-associated antigens can expand the range of surface proteins amenable to CAR-T cell-based therapies in solid tumors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-013120","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T13:15:16Z","timestamp":1763471716000},"page":"e013120","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["CAR-T cell therapy targeting MUC17 in gastric 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