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Antibody\u2010recruiting molecules (ARMs) offer an alternative strategy by harnessing endogenous antibodies to induce immune\u2010mediated tumor clearance; however, their therapeutic efficacy is often constrained by insufficient antibody recruitment arising from weak hapten\u2013antibody interactions. Here we report a receptor\u2010triggered supramolecular assembly strategy that converts monovalent antibody recruiters into multivalent immunotherapeutic platforms directly on cancer cell surfaces. An EGFR\u2010targeting peptide (GE11) was conjugated with a dinitrophenyl (DNP) hapten and a short self\u2010assembly motif to afford a monomeric construct that undergoes EGFR\u2010mediated in situ self\u2010assembly into fibrillar networks on EGFR\u2010overexpressing cells. This receptor\u2010guided supramolecular transformation generates a high\u2010density multivalent display of haptens on the cell membrane, enabling efficient recruitment of endogenous anti\u2010DNP antibodies. The resulting assemblies induce potent complement\u2010dependent cytotoxicity (CDC) against EGFR\u2010positive cancer cells in vitro and produce significant antitumor efficacy in tumor\u2010bearing mouse models with minimal systemic toxicity. This work establishes receptor\u2010mediated peptide self\u2010assembly as a general supramolecular strategy for transforming monovalent antibody recruiters into multivalent immunotherapeutic platforms, providing a new framework for the design of selective ARMs for cancer immunotherapy.<\/jats:p>","DOI":"10.1002\/advs.78074","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:02:48Z","timestamp":1790802168000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Receptor\u2010Triggered Peptide Self\u2010Assembly Enables Multivalent Recruitment of Endogenous Antibodies for Cancer Immunotherapy"],"prefix":"10.1002","author":[{"given":"Yihui","family":"Wang","sequence":"first","affiliation":[{"name":"Hunan Provincial Key Laboratory of Animal Models and Molecular Medicine State Key Laboratory of Chemo\/Bio\u2010Sensing and Chemometrics School of Biomedical Sciences Hunan University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1496-8800","authenticated-orcid":false,"given":"Xia","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cardiology The Central Hospital of Xiangtan (The affiliated Hospital of Hunan University), Hunan University Xiangtan Hunan China"},{"name":"Shenzhen Research Institute of Hunan University  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenguang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Animal Models and Molecular Medicine State Key Laboratory of Chemo\/Bio\u2010Sensing and Chemometrics School of Biomedical Sciences Hunan University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Han","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Animal Models and Molecular Medicine State Key Laboratory of Chemo\/Bio\u2010Sensing and Chemometrics School of Biomedical Sciences Hunan University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9346-6456","authenticated-orcid":false,"given":"Wensha","family":"Xie","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Animal Models and Molecular Medicine State Key Laboratory of Chemo\/Bio\u2010Sensing and Chemometrics School of Biomedical Sciences Hunan University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2831-0388","authenticated-orcid":false,"given":"Dan","family":"Yuan","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Animal Models and Molecular Medicine State Key Laboratory of Chemo\/Bio\u2010Sensing and Chemometrics School of Biomedical Sciences Hunan University  Changsha Hunan 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