{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T09:54:59Z","timestamp":1791453299554,"version":"4.3.3"},"reference-count":46,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"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":["52233013"],"award-info":[{"award-number":["52233013"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82304387"],"award-info":[{"award-number":["82304387"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82003579"],"award-info":[{"award-number":["82003579"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["226\u20102023\u201000059"],"award-info":[{"award-number":["226\u20102023\u201000059"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LQ21H300005"],"award-info":[{"award-number":["LQ21H300005"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012476","name":"Fundamental Research Funds for Central Universities of the Central South University","doi-asserted-by":"publisher","award":["2021FZZX001\u201046"],"award-info":[{"award-number":["2021FZZX001\u201046"]}],"id":[{"id":"10.13039\/501100012476","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":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hematopoietic progenitor pinase1 (HPK1) knockout has been identified as an efficient route to enhance anti\u2010tumor immune response. Here, this work develops an oral proteolysis targeting chimera (PROTAC) targeting HPK1 to efficiently and selectively degrade HPK1 to augment immunotherapeutic outcomes. In a postoperative tumor model of human cervical cancer in NSG mice, the orally\u2010administrated PROTAC can reach tumors, down\u2010regulate HPK1 levels in locally\u2010administrated CAR\u2010T cells, and promote their efficiency in inhibiting solid tumor recurrence, achieving 50% partial response (PR) and 50% complete response (CR). In addition, oral administration of PROTAC can amplify the suppression capability of the anti\u2010PD\u2010L1 antibody on the growth of CT26 solid tumors in BALB\/c mice by promoting the infiltration of CD45\u2010positive immune cells from 0.7% to 1.5% and CD3\u2010positive T cells from 0.2% to 0.5% within the tumors.<\/jats:p>","DOI":"10.1002\/adma.202411454","type":"journal-article","created":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T01:49:22Z","timestamp":1732153762000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["An Oral PROTAC Targeting HPK1 Degradation Potentiates Anti\u2010Solid Tumor Immunity"],"prefix":"10.1002","volume":"37","author":[{"given":"Yuejun","family":"Yao","sequence":"first","affiliation":[{"name":"National Key Laboratory of Advanced Drug Delivery and Release Systems College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"},{"name":"Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"},{"name":"Jinhua Institute of Zhejiang University  Jinhua 321299 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingfei","family":"Wu","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Advanced Drug Delivery and Release Systems College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"},{"name":"Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfang","family":"Wang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Advanced Drug Delivery and Release Systems College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"},{"name":"Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"},{"name":"Jinhua Institute of Zhejiang University  Jinhua 321299 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyan","family":"Liao","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Advanced Drug Delivery and Release Systems College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"},{"name":"Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"},{"name":"Jinhua Institute of Zhejiang University  Jinhua 321299 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinxian","family":"Yang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Advanced Drug Delivery and Release Systems College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"},{"name":"Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"},{"name":"Jinhua Institute of Zhejiang University  Jinhua 321299 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Liu","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Advanced Drug Delivery and Release Systems College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"},{"name":"Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"},{"name":"Jinhua Institute of Zhejiang University  Jinhua 321299 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Shi","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Advanced Drug Delivery and Release Systems College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"},{"name":"Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"},{"name":"Jinhua Institute of Zhejiang University  Jinhua 321299 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology The First Affiliated Hospital School of Medicine Zhejiang University  Hangzhou 310003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinwei","family":"Wei","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Advanced Drug Delivery and Release Systems College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"},{"name":"Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"},{"name":"Jinhua Institute of Zhejiang University  Jinhua 321299 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianchang","family":"Xu","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Advanced Drug Delivery and Release Systems College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"},{"name":"Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"},{"name":"Jinhua Institute of Zhejiang University  Jinhua 321299 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yugang","family":"Guo","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Advanced Drug Delivery and Release Systems College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"},{"name":"Institute of Drug Metabolism and Pharmaceutical Analysis College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowu","family":"Dong","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Advanced Drug Delivery and Release Systems College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"},{"name":"Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"},{"name":"Department of Pharmacy Second Affiliated Hospital Zhejiang University School of Medicine Zhejiang University  Hangzhou 310009 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxin","family":"Che","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Advanced Drug Delivery and Release Systems College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"},{"name":"Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Advanced Drug Delivery and Release Systems College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"},{"name":"Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"},{"name":"Jinhua Institute of Zhejiang University  Jinhua 321299 China"},{"name":"Department of Pharmacy Second Affiliated Hospital Zhejiang University School of Medicine Zhejiang University  Hangzhou 310009 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2947-4456","authenticated-orcid":false,"given":"Zhen","family":"Gu","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Advanced Drug Delivery and Release Systems College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"},{"name":"Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"},{"name":"Jinhua Institute of Zhejiang University  Jinhua 321299 China"},{"name":"Engineering Research Center of Innovative Anticancer Drugs Ministry of Education  Hangzhou 310000 China"},{"name":"MOE Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and Engineering Zhejiang University  Hangzhou 310027 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,20]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-021-00712-1"},{"key":"e_1_2_8_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/s44222-023-00031-x"},{"key":"e_1_2_8_1_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2015.03.001"},{"key":"e_1_2_8_1_4","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03704-y"},{"key":"e_1_2_8_1_5","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-00940-2"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-022-00689-z"},{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-00850-9"},{"key":"e_1_2_8_2_3","doi-asserted-by":"publisher","DOI":"10.1126\/science.abp8933"},{"key":"e_1_2_8_2_4","first-page":"24","volume":"7","author":"Ueda T.","year":"2023","journal-title":"Nat. Biomed. Eng."},{"key":"e_1_2_8_2_5","doi-asserted-by":"publisher","DOI":"10.1016\/j.medj.2022.12.001"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-021-00189-2"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202009489"},{"key":"e_1_2_8_3_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2021.06.012"},{"key":"e_1_2_8_3_4","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00823-w"},{"key":"e_1_2_8_3_5","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S239398"},{"key":"e_1_2_8_3_6","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf2807"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-020-01501-x"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aba1786"},{"key":"e_1_2_8_4_3","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0985-x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ai.2015.09.006"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.09.012"},{"key":"e_1_2_8_5_3","doi-asserted-by":"publisher","DOI":"10.1080\/13543776.2021.1924671"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/14728222.2024.2344697"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-012-8319-1"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2020.08.001"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-001402"},{"key":"e_1_2_8_7_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2022.114819"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41578-019-0156-6"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s44258-023-00006-y"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-022-01248-4"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1039\/D2CS00193D"},{"key":"e_1_2_8_9_3","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0668-z"},{"key":"e_1_2_8_9_4","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32050-4"},{"key":"e_1_2_8_9_5","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-021-00365-x"},{"key":"e_1_2_8_9_6","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-00999-9"},{"key":"e_1_2_8_10_1","unstructured":"J. L. Z. W. S.Xu 2021 WO2021000925A1."},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1416"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.05.011"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.0c00660"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-018-0319-4"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.01.024"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-021-00371-6"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mattod.2023.01.002"},{"key":"e_1_2_8_17_2","doi-asserted-by":"crossref","unstructured":"b)B.Deng S.Liu Y.Wang B.Ali N.Kong T.Xie S.Koo J.Ouyang W.Tao 2024 36 2306081.","DOI":"10.1002\/adma.202306081"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-024-00920-9"},{"key":"e_1_2_8_18_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21818"}],"container-title":["Advanced Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.202411454","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adma.202411454","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.202411454","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T09:35:25Z","timestamp":1791452125000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adma.202411454"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,20]]},"references-count":46,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1002\/adma.202411454"],"URL":"https:\/\/doi.org\/10.1002\/adma.202411454","archive":["Portico"],"relation":{},"ISSN":["0935-9648","1521-4095"],"issn-type":[{"value":"0935-9648","type":"print"},{"value":"1521-4095","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,20]]},"assertion":[{"value":"2024-08-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2411454"}}