{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:42:22Z","timestamp":1772152942694,"version":"3.50.1"},"reference-count":45,"publisher":"Wiley","issue":"25","license":[{"start":{"date-parts":[[2021,5,8]],"date-time":"2021-05-08T00:00:00Z","timestamp":1620432000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008235","name":"School of Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008235","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007890","name":"University of North Carolina at Chapel Hill","doi-asserted-by":"publisher","award":["CA16086"],"award-info":[{"award-number":["CA16086"]}],"id":[{"id":"10.13039\/100007890","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007890","name":"University of North Carolina at Chapel Hill","doi-asserted-by":"publisher","award":["P30CA016086"],"award-info":[{"award-number":["P30CA016086"]}],"id":[{"id":"10.13039\/100007890","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008615","name":"Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008615","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006808","name":"University of North Carolina","doi-asserted-by":"publisher","award":["R01CA178748"],"award-info":[{"award-number":["R01CA178748"]}],"id":[{"id":"10.13039\/100006808","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Materials"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease that results from autoreactive T cells destroying insulin\u2010producing pancreatic beta (\u03b2) cells. The development of T1DM is associated with the deficiency of co\u2010inhibitory immune checkpoint ligands (e.g., PD\u2010L1, CD86, and Gal\u20109) in \u03b2 cells. Here, a new translational approach based on metabolic glycoengineering and bioorthogonal click chemistry, which bioengineers \u03b2 cells with co\u2010inhibitory immune checkpoint molecules that induce antigen\u2010specific immunotolerance and reverse early\u2010onset hyperglycemia is reported. To achieve this goal, a subcutaneous injectable acellular pancreatic extracellular matrix platform for localizing the bioengineered \u03b2 cells while creating a pancreas\u2010like immunogenic microenvironment, in which the autoreactive T cells can interface with the \u03b2 cells, is devised.<\/jats:p>","DOI":"10.1002\/adma.202101253","type":"journal-article","created":{"date-parts":[[2021,5,9]],"date-time":"2021-05-09T02:52:48Z","timestamp":1620528768000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Immune Checkpoint\u2010Bioengineered Beta Cell Vaccine Reverses Early\u2010Onset Type 1 Diabetes"],"prefix":"10.1002","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9341-0479","authenticated-orcid":false,"given":"Kin Man","family":"Au","sequence":"first","affiliation":[{"name":"Laboratory of Nano\u2010 and Translational Medicine Carolina Center for Cancer Nanotechnology Excellence Carolina Institute of Nanomedicine University of North Carolina at Chapel Hill  Chapel Hill NC 27599 USA"},{"name":"Department of Radiation Oncology Lineberger Comprehensive Cancer Center University of North Carolina at Chapel Hill  Chapel Hill NC 27599 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusra","family":"Medik","sequence":"additional","affiliation":[{"name":"Laboratory of Nano\u2010 and Translational Medicine Carolina Center for Cancer Nanotechnology Excellence Carolina Institute of Nanomedicine University of North Carolina at Chapel Hill  Chapel Hill NC 27599 USA"},{"name":"Department of Radiation Oncology Lineberger Comprehensive Cancer Center University of North Carolina at Chapel Hill  Chapel Hill NC 27599 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Ke","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology School of Medicine University of North Carolina at Chapel Hill  Chapel Hill NC 27599 USA"},{"name":"Lineberger Comprehensive Cancer Center University of North Carolina at Chapel Hill  Chapel Hill NC 27599 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roland","family":"Tisch","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology School of Medicine University of North Carolina at Chapel Hill  Chapel Hill NC 27599 USA"},{"name":"Lineberger Comprehensive Cancer Center University of North Carolina at Chapel Hill  Chapel Hill NC 27599 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew Z.","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Nano\u2010 and Translational Medicine Carolina Center for Cancer Nanotechnology Excellence Carolina Institute of Nanomedicine University of North Carolina at Chapel Hill  Chapel Hill NC 27599 USA"},{"name":"Department of Radiation Oncology Lineberger Comprehensive Cancer Center University of North Carolina at Chapel Hill  Chapel Hill NC 27599 USA"},{"name":"Lineberger Comprehensive Cancer Center University of North Carolina at Chapel Hill  Chapel Hill NC 27599 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,5,8]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60591-7"},{"key":"e_1_2_8_1_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00003.2010"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.16"},{"key":"e_1_2_8_3_1","first-page":"183","volume":"17","author":"Tomita T.","year":"2017","journal-title":"Bosnian J. Basic Med. Sci."},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aam7543"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-1419"},{"key":"e_1_2_8_6_1","volume-title":"Global Report on Diabetes","author":"Roglic G.","year":"2016"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-1391"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.2337\/db10-0560"},{"key":"e_1_2_8_7_3","doi-asserted-by":"publisher","DOI":"10.1002\/pdi.1764"},{"key":"e_1_2_8_7_4","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00392"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-bioeng-110315-020137"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02934736"},{"key":"e_1_2_8_8_3","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.21.120601.141110"},{"key":"e_1_2_8_8_4","doi-asserted-by":"publisher","DOI":"10.1126\/science.1972595"},{"key":"e_1_2_8_8_5","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2622"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-307311"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4571"},{"key":"e_1_2_8_9_3","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901038"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e31818c6e64"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20022125"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.5.2444"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2011-1579"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41570-019-0126-y"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwp115"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9SC03368H"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0911116107"},{"key":"e_1_2_8_15_3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0707090104"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4030"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/nn901319y"},{"key":"e_1_2_8_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2012.03.065"},{"key":"e_1_2_8_18_1","doi-asserted-by":"crossref","unstructured":"T. N.Schumacher M. T.Heemels J. J.Neefjes W. M.Kast |C. J.Melief H. L.Ploegh Cell1990 62 563.","DOI":"10.1016\/0092-8674(90)90020-F"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/2045-3701-4-51"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2016.11.007"},{"key":"e_1_2_8_20_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.2000.00121.x"},{"key":"e_1_2_8_20_3","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.11.7660"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3405"},{"key":"e_1_2_8_22_1","first-page":"6","volume":"1","author":"Tieu R.","year":"2014","journal-title":"Austin Virol. Retrovirol."},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-1620"},{"key":"e_1_2_8_23_2","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2016.1249561"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2010.05.004"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41563-018-0099-0"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-28857-1"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-018-0231-0"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201907692"}],"container-title":["Advanced Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.202101253","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adma.202101253","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.202101253","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T11:14:42Z","timestamp":1759749282000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adma.202101253"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,8]]},"references-count":45,"journal-issue":{"issue":"25","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1002\/adma.202101253"],"URL":"https:\/\/doi.org\/10.1002\/adma.202101253","archive":["Portico"],"relation":{},"ISSN":["0935-9648","1521-4095"],"issn-type":[{"value":"0935-9648","type":"print"},{"value":"1521-4095","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,8]]},"assertion":[{"value":"2021-02-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2101253"}}