{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T07:02:22Z","timestamp":1780038142017,"version":"3.53.1"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Mesothelin (MSLN) is a GPI-anchored cell surface glycoprotein that is overexpressed in various solid tumors, including mesothelioma, triple-negative breast cancer, colon, ovarian and pancreatic cancer, with restricted normal tissue expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To explore the immunogenicity and immunotherapeutic potential of MSLN to T cells with native receptor specificity, 29 individuals of diverse HLA backgrounds were interrogated for T cell activity against MSLN.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty one (72%) subjects (21\/29) mounted a specific T cell response when repetitively challenged with MSLN antigen. Reactive cells were Th1-polarized, polyfunctional, predominantly detected in the CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell compartment and cytotoxic toward autologous and MSLN\n                      <jats:sup>+<\/jats:sup>\n                      \/HLA-matched tumor cell lines in conventional 2D\n                      <jats:italic>in vitro<\/jats:italic>\n                      assays. Furthermore, these cells produced anti-tumor effects in a novel 3D tumor spheroid model system established to evaluate the potency of reactive cells against tumors including pancreatic, cervical, and colorectal cancer and mesothelioma.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These preclinical findings lay the groundwork for further exploration of MSLN as a potential immunotherapeutic target for T cells via the native T cell receptor.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1853409","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T06:10:26Z","timestamp":1780035026000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluating mesothelin as an immunotherapeutic target for endogenous T cells"],"prefix":"10.3389","volume":"17","author":[{"given":"Kiriakos","family":"Koukoulias","sequence":"first","affiliation":[{"name":"Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children\u2019s Hospital, and the Methodist Hospital","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryu","family":"Yanagisawa","sequence":"additional","affiliation":[{"name":"Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children\u2019s Hospital, and the Methodist Hospital","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro G.","family":"Torres Chavez","sequence":"additional","affiliation":[{"name":"Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children\u2019s Hospital, and the Methodist Hospital","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penelope G.","family":"Papayanni","sequence":"additional","affiliation":[{"name":"Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children\u2019s Hospital, and the Methodist Hospital","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yovana","family":"Velazquez","sequence":"additional","affiliation":[{"name":"Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children\u2019s Hospital, and the Methodist Hospital","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun-Sung","family":"Lee","sequence":"additional","affiliation":[{"name":"Systems Onco-Immunology Lab, David J. 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