{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:26:50Z","timestamp":1787016410526,"version":"build-2736575974"},"reference-count":48,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"16","funder":[{"DOI":"10.13039\/501100001381","name":"National Research Foundation Singapore","doi-asserted-by":"crossref","award":["NRF-NRFF12-2020-0007"],"award-info":[{"award-number":["NRF-NRFF12-2020-0007"]}],"id":[{"id":"10.13039\/501100001381","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NRF Competitive Research Programme"},{"name":"Singapore Ministry of Health\u2019s National Medical Research Council","award":["OF-IRG23jul-0080"],"award-info":[{"award-number":["OF-IRG23jul-0080"]}]},{"name":"Singapore Ministry of Health\u2019s National Medical Research Council","award":["MOH-001573"],"award-info":[{"award-number":["MOH-001573"]}]},{"name":"Ministry of Education","award":["T2EP30123-0038"],"award-info":[{"award-number":["T2EP30123-0038"]}]},{"name":"STAR Award","award":["MOH-001090-00"],"award-info":[{"award-number":["MOH-001090-00"]}]},{"name":"Institute for Health Innovation and Technology, nstitute for Health Innovation & Technology"},{"name":"National University of Singapore (NUS) Research Scholarship from the Singapore Ministry of Education"},{"name":"National University of Singapore (NUS) Research Scholarship from the Singapore Ministry of Education"},{"name":"LCG VICTORY","award":["NMRC\/OFLCG\/003\/2018"],"award-info":[{"award-number":["NMRC\/OFLCG\/003\/2018"]}]},{"name":"NMRC CS-IRG New Investigator Grant"},{"name":"The MOH Foundation"},{"name":"NUS President\u2019s Graduate Fellowship"}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,4,17]]},"abstract":"<jats:p>\n                    A major challenge in advancing neoantigen-targeted therapies lies in the limited capacity of predicted neoantigens to robustly activate CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, emphasizing the critical need for comprehensive functional validation before patient vaccination. Here, we provide a direct comparison of neoantigen-specific T cell responses between vaccinated patients with cancer and HLA-matched healthy donors. Despite vaccination, patient-derived T cells recognized only a small fraction of predicted neoantigens, whereas healthy donor T cells consistently exhibited broader and more robust neoantigen reactivity. Furthermore, we successfully expanded neoantigen-specific T cells from allogeneic donors, revealing that their T cell receptors (TCRs) can recognize targets that the patient\u2019s own T cells fail to engage with, partly due to poor T cell fitness. Collectively, these results indicate that cancer vaccines may be insufficient to overcome intrinsic defects in patient-derived T cell responses, supporting the use of healthy donor-derived TCRs as a complementary approach.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adz1156","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T18:00:21Z","timestamp":1776448821000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":2,"title":["Healthy donor T cell receptors expand functional neoantigen recognition beyond patient vaccination"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2809-0230","authenticated-orcid":true,"given":"Hong Kai","family":"Teo","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, Singapore."},{"name":"Institute for Health Innovation &amp; Technology (iHealthtech), National University of Singapore, Singapore, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0217-7956","authenticated-orcid":true,"given":"Shuting","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, Singapore."},{"name":"Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thamizhanban","family":"Manoharan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3809-0967","authenticated-orcid":true,"given":"Yi","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, National University of Singapore, Singapore, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3235-4573","authenticated-orcid":true,"given":"Cyrus Zai Ming","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, Singapore."},{"name":"Institute for Health Innovation &amp; Technology (iHealthtech), National University of Singapore, Singapore, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4004-043X","authenticated-orcid":true,"given":"Soon Chai","family":"Loo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1301-6661","authenticated-orcid":true,"given":"Zhewang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, National University of Singapore, Singapore, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0502-3313","authenticated-orcid":true,"given":"Jiaqi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, National University of Singapore, Singapore, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8361-6761","authenticated-orcid":true,"given":"Who-Whong","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-Lin","family":"Koo","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malini","family":"Rethnam","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, Singapore."},{"name":"Institute for Health Innovation &amp; Technology (iHealthtech), National University of Singapore, Singapore, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4024-2736","authenticated-orcid":true,"given":"Choon Kong","family":"Yap","sequence":"additional","affiliation":[{"name":"Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei-En","family":"Siew","sequence":"additional","affiliation":[{"name":"Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5318-9327","authenticated-orcid":true,"given":"Gwyneth Shook-Ting","family":"Soon","sequence":"additional","affiliation":[{"name":"Division of Colorectal Surgery, Department of Surgery, National University Hospital, Singapore, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai-Kit","family":"Cheong","sequence":"additional","affiliation":[{"name":"Division of Colorectal Surgery, Department of Surgery, National University Hospital, Singapore, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0767-7922","authenticated-orcid":true,"given":"Kai-Yin","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Colorectal Surgery, Department of Surgery, National University Hospital, Singapore, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1923-0653","authenticated-orcid":true,"given":"Ian Jse-Wei","family":"Tan","sequence":"additional","affiliation":[{"name":"Division of Colorectal Surgery, Department of Surgery, National University Hospital, Singapore, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6221-3974","authenticated-orcid":true,"given":"Bettina","family":"Lieske","sequence":"additional","affiliation":[{"name":"Division of Colorectal Surgery, Department of Surgery, National University Hospital, Singapore, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ker-Kan","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore."},{"name":"Division of Colorectal Surgery, Department of Surgery, National University Hospital, Singapore, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han Chong","family":"Toh","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4951-0354","authenticated-orcid":true,"given":"Iain Bee Huat","family":"Tan","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore."},{"name":"Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore."},{"name":"Singapore Duke-NUS Medical School, Singapore, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2099-719X","authenticated-orcid":true,"given":"Gloryn","family":"Chia","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, Singapore."},{"name":"Institute for Health Innovation &amp; Technology (iHealthtech), National University of Singapore, Singapore, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.07.012"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-021-00247-z"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04735-9"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.01.010"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4051"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)02268-7"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-021-00387-y"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature22991"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature23003"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2537-9"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-01206-4"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06063-y"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.08.053"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0792-9"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03109-0"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad1253"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.6960"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-2680"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01718"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf2288"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.09.015"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0130-2"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-019-0170-6"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-003087"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.07.009"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3161"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1609279"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-21-3717"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2018.03.012"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.806"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi1110s43"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu548"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gpb.2020.02.001"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.129684.111"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-018-0051-x"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0974-4"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-19-0464"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv639"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa379"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-021-03096-y"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-020-03624-0"},{"key":"e_1_3_2_45_2","first-page":"99","article-title":"Human leukocyte antigen allele and haplotype frequencies in Singapore bone marrow donors and cord blood units","volume":"5","author":"Yu-Jin A. N.","year":"2022","unstructured":"A. N. Yu-Jin, G. B. Moshi, A. Prasath, M. Chan, P. L. Michelle, L. C. K. Charles, L. Cho, V. Voon, S. Z. Jing, P. C. Yen, A. Y. L. Ho, Human leukocyte antigen allele and haplotype frequencies in Singapore bone marrow donors and cord blood units. Blood Cell Ther. 5, 99\u2013106 (2022).","journal-title":"Blood Cell Ther."},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2023-008402"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3979"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3364"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac190"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.adz1156","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T15:55:11Z","timestamp":1780588511000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.adz1156"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,17]]},"references-count":48,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2026,4,17]]}},"alternative-id":["10.1126\/sciadv.adz1156"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.adz1156","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,17]]},"assertion":[{"value":"2025-05-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadz1156"}}