{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:50:25Z","timestamp":1791521425533,"version":"4.3.4"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"\n Introduction<\/jats:title>\n Tumor heterogeneity and signaling redundancy limit the efficacy of monospecific antibody therapies in solid malignancies. Here we used our platform of glyco-humanized polyclonal antibodies (GH-pAb), to investigate whether targeting multiple tumor-associated antigens provides integrated anti-tumor activity.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n GH-pAb (hereinafter XON7) were generated by immunization of double-knockout pigs with human tumor cells. Antigen specificity of XON7 was assessed using a human proteome array and validated by ELISA. Anti-tumor mechanisms were evaluated\n in vitro<\/jats:italic>\n on 2D or 3D-cultures. Efficacy was tested\n in vivo<\/jats:italic>\n in cell or patient-derived xenograft (CDX, PDX), in chicken chorioallantoic membrane (CAM) model, and in orthotopic\/metastatic triple negative breast cancer (TNBC) models.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n XON7 demonstrated tumor-restricted binding across tissue microarrays without detectable staining in matched normal tissues. Mechanistically, XON7 induced potent cytotoxicity across a wide tumor panel through complement activation, apoptosis, and antibody-dependent cellular phagocytosis. Proteome profiling identified predominant reactivities against solute carrier family 3 member 2 (SLC3A2), annexin A2 (ANXA2), and cytoskeleton-associated protein 4 (CKAP4), all broadly expressed tumor-associated surface proteins. Immunodepletion experiments revealed that concurrent targeting of these three targets was required to maintain the full anti-proliferative activity of XON7, supporting a multitarget-dependent mechanism. XON7 also induced released of high-mobility group protein box 1 (HMGB1), a hallmark of immunogenic cell death.\n In vivo<\/jats:italic>\n , XON7 inhibited tumor growth in CDX and PDX models, and markedly reduced metastatic dissemination in orthotopic and intravenous TNBC models. In a CAM model, XON7 synergized with PD-1 blockade, enhancing tumor control and promoting macrophage polarization toward a M1 phenotype.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n By simultaneously engaging non-redundant tumor pathways and reshaping the tumor microenvironment, XON7 may overcome key resistance mechanisms of solid tumors.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fonc.2026.1947593","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:26:26Z","timestamp":1791519986000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Tumor-antigen-specific polyclonal antibodies suppress tumor growth and metastasis in heterogeneous solid tumors"],"prefix":"10.3389","volume":"16","author":[{"given":"Carine","family":"Ciron","sequence":"first","affiliation":[{"name":"Xenothera","place":["Nantes, 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of Anxa2 in cancer progression: highlights on its novel regulatory mechanism\n \n \n \n Wang\n T\n \n \n Wang\n Z\n \n \n Niu\n R\n \n \n Wang\n L\n \n \n 10.20892\/J.ISSN.2095-3941.2019.0228\n Cancer Biol Med\n 16\n 2019","DOI":"10.20892\/j.issn.2095-3941.2019.0228"},{"key":"B40","doi-asserted-by":"publisher","first-page":"2994","DOI":"10.1002\/1878-0261.12851","article-title":"Targeting immunogenic cell death in cancer","volume":"14","author":"Ahmed","year":"2020","journal-title":"Mol Oncol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/nri.2016.107","article-title":"Immunogenic cell death in cancer and infectious disease","volume":"17","author":"Galluzzi","year":"2017","journal-title":"Nat Rev Immunol"},{"key":"B42","doi-asserted-by":"crossref","unstructured":"Emerging role of immunogenic cell death in cancer immunotherapy\n \n \n \n Arimoto\n KI\n \n \n Miyauchi\n S\n \n \n Liu\n M\n \n \n Zhang\n DE\n \n \n 10.3389\/FIMMU.2024.1390263\n Front 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