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We engineer platinum(IV)\u2013antibody conjugates [Pt-ADCs (platinum-based antibody\u2013drug conjugates)] that confine a \u2018metal immune effect\u2019 to tumors while reducing off-tumor exposure. Site-specific glycoengineering installs redox-responsive Pt(IV) prodrugs at defined drug-to-antibody ratios, yielding homogeneous conjugates. Mechanistic profiling shows that cisplatin-derived, but not oxaliplatin-derived, payloads undergo efficient reductive activation in the tumor milieu; cinnamate-capped variants optimize serum stability, intratumoral release, and immunostimulatory signaling. In syngeneic models, Pt-ADCs deliver a low dose of cinnamate-capped Pt to upregulate major histocompatibility complex class I on tumor cells, expand tumor-reactive T-cell receptor clonotypes, and synergize with PD-1 blockade to suppress tumor growth, with minimal systemic toxicity. These findings position Pt-ADCs as a detoxified, immunogenic modality that uncouples immunogenic priming from high-dose cytotoxicity and offers a tractable path to rational dosing in chemo-immunotherapy combinations.<\/jats:p>","DOI":"10.1093\/nsr\/nwag202","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T11:41:41Z","timestamp":1775043701000},"source":"Crossref","is-referenced-by-count":6,"title":["Uncoupling tumor immunogenicity from cell death with platinum(IV)\u2013antibody conjugates"],"prefix":"10.1093","volume":"13","author":[{"given":"Liu-Yi","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210023 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhao","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key 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