{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T15:27:42Z","timestamp":1786548462908,"version":"build-2736575974"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005089","name":"Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["L254035"],"award-info":[{"award-number":["L254035"]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Center of Technology Innovation for Biopharmaceuticals","award":["NCTIB2023XB01014"],"award-info":[{"award-number":["NCTIB2023XB01014"]}]},{"name":"High Innovation Plan","award":["202504841086"],"award-info":[{"award-number":["202504841086"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["HY2021-7"],"award-info":[{"award-number":["HY2021-7"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>CD93 is an emerging immune checkpoint. Blocking its interaction with insulin-like growth factor-binding protein-7 (IGFBP7) restores antitumor immunity, yet discovering high-affinity antibodies against this specific functional epitope remains a formidable challenge for traditional methods.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We employed a proprietary generative artificial intelligence (AI) model, GeoFlow, to de novo design antibodies targeting the predicted binding epitope of a reference antibody 7F3. A library constructed from 105 sequences was screened via phage display, and the lead candidate, 7-4_com10, was validated through biolayer interferometry, flow cytometry, and in vivo efficacy studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>To dissect the contribution of endothelial CD93 to immunotherapy resistance, we utilized an endothelial-specific conditional knockout model in MB49 bladder cancer, where the loss of endothelial CD93 significantly sensitized tumors to PD-1 inhibition. The genetic findings identified endothelial CD93 as a fundamental driver of immunotherapy resistance and provided the rationale for our GeoFlow generative AI platform, which was employed to de novo design ~105 candidates targeting the IGFBP7-binding interface on CD93. Our lead candidate, 7-4_com10, demonstrated superior affinity and more potent functional blockade of the CD93\u2013IGFBP7 axis compared to the reference 7F3. Crucially, 7-4_com10 sensitized H22 solid tumors to anti-PD-1 therapy in vivo, which confirmed that 7-4_com10 successfully targeted the identified immunosuppressive axis and pharmacologically phenocopied the benefits of genetic endothelial ablation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study validated generative AI for designing epitope-specific antibodies with superior potency, offering a robust candidate for next-generation immunotherapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/abt\/tbag019","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T11:31:25Z","timestamp":1777289485000},"page":"323-331","source":"Crossref","is-referenced-by-count":0,"title":["Generative AI\u2013driven\n                    <i>de novo<\/i>\n                    design of high-affinity, epitope-specific antibodies targeting the CD93\u2013IGFBP7 axis for cancer immunotherapy"],"prefix":"10.1093","volume":"9","author":[{"given":"Yixin","family":"Qian","sequence":"first","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences, Health Science Center, Peking University , Beijing 100191 ,","place":["PR China"]},{"name":"State Key Laboratory of Molecular Oncology, Frontiers Science Center for Cancer Integrative Omics, Peking University International Cancer Institute, Peking University , Beijing 100191 ,","place":["PR China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youxin","family":"Feng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Oncology, Frontiers Science Center for Cancer Integrative Omics, Peking University International Cancer Institute, Peking University , Beijing 100191 ,","place":["PR 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