{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T07:54:20Z","timestamp":1781855660041,"version":"3.54.5"},"reference-count":23,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32371470"],"award-info":[{"award-number":["32371470"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["RCYX20200714114736146"],"award-info":[{"award-number":["RCYX20200714114736146"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Adoptive T cell therapy holds great promise for the treatment of solid tumors but remains constrained by tumor heterogeneity, inefficient neoantigen targeting, and the complexity of T cell manufacturing. Here, we present a patient\u2010specific, broadly applicable platform using physically inactivated tumor organoids (PIOs) to generate tumor\u2010specific cytotoxic T cells ex vivo. Derived from droplet\u2010engineered tumor organoids (DEOs), PIOs preserve the full antigenic repertoire of the patient's tumor without requiring synthetic peptides, antigen\u2010presenting cells, or neoantigen prediction. Using matched tumor tissue and PBMCs from colorectal and liver cancer patients, we show that PIOs activate and expand tumor\u2010specific T cells with enhanced infiltration, selective cytotoxicity, and robust secretion of IFN\u2010\u03b3 and IL\u20102. Multi\u2010round PIO stimulation achieves 80\u2013400\u2010fold expansion of CD8\n                    <jats:sup>+<\/jats:sup>\n                    CD137\n                    <jats:sup>+<\/jats:sup>\n                    T cells within two weeks. Transcriptomic and epigenetic profiling suggest that PIOs modulate T cell programs linked to migration and persistence. This work redefines tumor organoids as immunotherapeutic materials and establishes a rapid, cost\u2010effective platform for personalized T cell manufacturing. Our findings provide a new translational route for adoptive cell therapy in solid tumors using patient\u2010derived materials.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202503992","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T09:10:28Z","timestamp":1778058628000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Physically Inactivated Tumor Organoids Enable Rapid and Personalized Enrichment of Cytotoxic T Cells for Solid Tumor Immunotherapy"],"prefix":"10.1002","volume":"15","author":[{"given":"Yu","family":"Zhang","sequence":"first","affiliation":[{"name":"Tsinghua Shenzhen International Graduate School (SIGS) Tsinghua University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Zhao","sequence":"additional","affiliation":[{"name":"Synorg Biotechnology (Shenzhen) Co. Ltd.  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhong","family":"Zeng","sequence":"additional","affiliation":[{"name":"Tsinghua Shenzhen International Graduate School (SIGS) Tsinghua University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zitian","family":"Wang","sequence":"additional","affiliation":[{"name":"Tsinghua Shenzhen International Graduate School (SIGS) Tsinghua University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyong","family":"Dai","sequence":"additional","affiliation":[{"name":"Tsinghua Shenzhen International Graduate School (SIGS) Tsinghua University  Shenzhen China"},{"name":"Synorg Biotechnology (Shenzhen) Co. Ltd.  Shenzhen China"},{"name":"Department of Physiology School of Medicine State Key Laboratory of Bioactive Molecules and Druggability Assessment and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research Jinan University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongde","family":"Cai","sequence":"additional","affiliation":[{"name":"Tsinghua Shenzhen International Graduate School (SIGS) Tsinghua University  Shenzhen China"},{"name":"Synorg Biotechnology (Shenzhen) Co. Ltd.  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruirui","family":"Qiao","sequence":"additional","affiliation":[{"name":"Australian Institute of Bioengineering &amp; Nanotechnology The University of Queensland  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingwen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rheumatism and Immunology Peking University Shenzhen Hospital  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter E.","family":"Lobie","sequence":"additional","affiliation":[{"name":"Tsinghua Shenzhen International Graduate School (SIGS) Tsinghua University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6649-171X","authenticated-orcid":false,"given":"Shaohua","family":"Ma","sequence":"additional","affiliation":[{"name":"Tsinghua Shenzhen International Graduate School (SIGS) Tsinghua University  Shenzhen China"},{"name":"Key Lab of Industrial Biocatalysis Ministry of Education Tsinghua University  Beijing China"},{"name":"HaploX Biotechnology  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.01.049"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2016.04.01"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aar1916"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2018.6"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-6611"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-018-0007-6"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19142-9"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2020.100161"},{"key":"e_1_2_9_10_1","doi-asserted-by":"crossref","unstructured":"W.Wang Y.Cai X.Dai et\u00a0al. Formulation and Characterization of Primary Tissue\u2010Derived Microfluidic Droplet\u2010Engineered Organoids v1(2025).","DOI":"10.17504\/protocols.io.yxmvmb77og3p\/v1"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.device.2024.100420"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2026.116987"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.07.009"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-024-03749-8"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-2680"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-002754"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-07-0092"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.62019"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aau5516"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4047"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41563-024-01825-z"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20658-3"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2021.05.016"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature22367"}],"container-title":["Advanced Healthcare Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202503992","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adhm.202503992","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202503992","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T07:42:05Z","timestamp":1781854925000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adhm.202503992"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":23,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/adhm.202503992"],"URL":"https:\/\/doi.org\/10.1002\/adhm.202503992","archive":["Portico"],"relation":{},"ISSN":["2192-2640","2192-2659"],"issn-type":[{"value":"2192-2640","type":"print"},{"value":"2192-2659","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"2025-08-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e03992"}}