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Traditional carrier\u2010protein conjugates often encounter issues such as epitope suppression and heterogeneous formulations. Herein, we present the design, synthesis, and immunological evaluation of a chemically defined, four\u2010component self\u2010adjuvanting glycoconjugate. This molecule combines multiple innate immune activation strategies into a single, unimolecular framework, incorporating (1) a synthetic Tn as the B\u2010cell epitope; (2) vizantin, a strong Mincle agonist, as an internal adjuvant; (3) rhamnose to attract endogenous antibodies for Fc\u03b3 receptor\u2013mediated uptake; and (4) mannose to target dendritic cells through CD206. By ensuring precise co\u2010delivery and synergistic activation of Mincle, Fc\u03b3 receptor, and CD206 pathways, this construct induces strong IgG switching, Th1\u2011type cytokine responses, and significant tumor suppression in mice. This research offers a versatile chemical approach for next\u2011generation TACA vaccines, illustrating how activating multiple innate pathways can overcome the longstanding limitations of carbohydrate\u2010based immunotherapies.<\/jats:p>","DOI":"10.1002\/advs.76235","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T19:41:18Z","timestamp":1782157278000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Chemically Defined Four\u2010Component Self\u2010Adjuvanting Tn Vaccine Activating Mincle, Fc\u03b3R, and CD206 for Enhanced Antitumor Immunity"],"prefix":"10.1002","volume":"13","author":[{"given":"Wenbo","family":"Ming","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Translational Chinese Medicine Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines International Institute for Translational Chinese Medicine School of Pharmaceutical Sciences Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Translational Chinese Medicine Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines International Institute for Translational Chinese Medicine School of Pharmaceutical Sciences Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Translational Chinese Medicine Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines International Institute for Translational Chinese Medicine School of Pharmaceutical Sciences Guangzhou University of Chinese Medicine  Guangzhou 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deying","family":"Yang","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Guangdong Medical University  Zhanjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Luo","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Translational Chinese Medicine Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines International Institute for Translational Chinese Medicine School of Pharmaceutical Sciences Guangzhou University of Chinese Medicine  Guangzhou China"},{"name":"Chinese Medicine Guangdong Laboratory  Hengqin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology College of Basic Medical Sciences Second Military Medical University  Shanghai 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the development of self\u2010adjuvanting carbohydrate vaccines two distinct antigenic strategies have emerged: Tn\u2010bearing glycopeptides and the minimal Tn antigen (Tn\u2010Ser\/Thr). While glycopeptides incorporate flanking amino acids that may contribute to the epitope's conformational stability the minimal Tn\u2010Ser\/Thr unit represents a simplified chemically defined approach to TACA targeting. Previous work from Boons Sucheck Seeberger and others have demonstrated the efficacy of the minimal Tn\u2010Ser\/Thr epitope in different synthetic frameworks. Journal of the American Chemical Society 132 (2010): 17236\u201317246; references 21 and 33. It should also be noted that the Tn antigen used in this study was in an N\u2010acetylated form. Previous studies have shown that this modification does not significantly compromise the antigenicity of the Tn epitope and is able to induce strong Tn\u2010specific immune responses and generate functionally active anti\u2010Tn antibodies in vivo indicating that the N\u2010acetylated Tn structure retains effective antigen recognition properties."},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.4.2849"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200324181"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262\u2010006\u20100225\u20108"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.76235","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.76235","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.76235","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T09:31:41Z","timestamp":1789723901000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.76235"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,22]]},"references-count":53,"journal-issue":{"issue":"52","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/advs.76235"],"URL":"https:\/\/doi.org\/10.1002\/advs.76235","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,22]]},"assertion":[{"value":"2026-01-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e76235"}}