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John Pickett Post-Doctoral Fellow Award"]}],"id":[{"id":"10.13039\/100007185","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007185","name":"University of California, Los Angeles","doi-asserted-by":"publisher","award":["UCLA BSCRC Innovation Award"],"award-info":[{"award-number":["UCLA BSCRC Innovation Award"]}],"id":[{"id":"10.13039\/100007185","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007557","name":"California Institute of Regenerative Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007557","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Exp Hematol Oncol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Aggressive subtypes of uterine endometrial carcinoma (UEC) often result in mortality due to recurrence of disease with chemoresistant tumor cells surrounded by an immune suppressive microenvironment. Current CAR-T cell therapies have shown limited efficacy in solid tumors, largely constrained by poor tumor infiltration, immune suppression, and the logistical limitations of autologous cell production, which hinder broad patient access.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study, we conducted comprehensive immunophenotyping of primary UEC patient samples and identified a therapeutic opportunity for CAR-engineered invariant natural killer T (CAR-NKT) cells capable of targeting both tumor cells and the immunosuppressive TME. Using a hematopoietic stem and progenitor cell (HSPC) engineering platform coupled with ex vivo differentiation culture, we generated allogeneic mesothelin-targeting CAR-NKT cells (\n                      <jats:sup>Allo<\/jats:sup>\n                      MCAR-NKT) with high purity and yield.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:sup>Allo<\/jats:sup>\n                      MCAR-NKT cells exhibited potent cytotoxic activity against UEC tumor cells and CD1d\u207a tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs). Importantly, compared to conventional CAR-T cells,\n                      <jats:sup>Allo<\/jats:sup>\n                      MCAR-NKT cells demonstrated an improved safety profile, showing no evidence of graft-versus-host disease (GvHD) and minimal cytokine release syndrome (CRS)-related toxicity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These findings highlight the potential of\n                      <jats:sup>Allo<\/jats:sup>\n                      MCAR-NKT cells as a safe and effective off-the-shelf cellular immunotherapy for the treatment of UEC and potentially other solid tumors characterized by an immunosuppressive microenvironment.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40164-026-00746-8","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T10:49:30Z","timestamp":1769683770000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Stem cell engineering for the generation of allogeneic CAR-directed natural killer T cells targeting endometrial carcinoma"],"prefix":"10.1186","volume":"15","author":[{"given":"Yan-Ruide","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella A.","family":"DiBernardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuning","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyuan","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Hon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauryn E.","family":"Ruegg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Neal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neda A.","family":"Moatamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanaz","family":"Memarzadeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,29]]},"reference":[{"key":"746_CR1","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3322\/caac.21871","volume":"75","author":"RL Siegel","year":"2025","unstructured":"Siegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A. 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Healthy donor PBMCs were obtained from the UCLA\/CFAR Virology Core Laboratory and HemaCare under informed consent and in compliance with federal and state regulations; no identifying information was provided. Primary UEC patient samples were collected at University of California, Los Angeles Medical Centers from consented patients through an IRB-approved protocol (UCLA IRB #10\u20130727, IRB#20-1659) and processed.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"L.Y. is a scientific advisor to AlzChem and Amberstone Biosciences, and a co-founder, stockholder, and advisory board member of Appia Bio. None of the declared companies contributed to or directed any of the research reported in this article. The remaining authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"14"}}