{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T17:44:28Z","timestamp":1785692668477,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,30]]},"group-title":"Cancer Biology","reference-count":57,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ABION Inc"},{"DOI":"10.13039\/501100004080","name":"Korea Drug Development Fund","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004080","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Center for Cancer Research, Intramural Program of the National Cancer Institute, NIH"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Small cell lung cancer (SCLC) remains a highly lethal disease with limited targetable surface antigens beyond delta-like ligand 3 (DLL3). We sought to systematically identify and validate tumor-selective cell-surface targets in relapsed SCLC. To this end, we developed an integrated proteogenomic pipeline combining single-cell RNA sequencing, combinatorial optimization, mass spectrometry\u2013based proteomics, and immunohistochemistry to systematically map the SCLC surfaceome of 49 tumors across 25 patients with relapsed SCLC. Using this approach we found claudin-3 (\n                  <jats:italic>CLDN3<\/jats:italic>\n                  ) to be a consistently expressed and tumor-selective antigen, with broader coverage than DLL3, which is the current clinical benchmark. CLDN3 was highly expressed across various treatment states, while maintaining low expression in most nonmalignant tissues. Functional validation using a novel CLDN3-specific monoclonal antibody (ABN501) demonstrated NK cell\u2013mediated cytotoxicity\n                  <jats:italic>in vitro<\/jats:italic>\n                  and tumor regression\n                  <jats:italic>in vivo<\/jats:italic>\n                  , as well as a favorable safety profile. These findings support clinical development of CLDN3-directed therapies and demonstrate the utility of integrated proteogenomic approaches for antigen discovery in solid tumors.\n                <\/jats:p>","DOI":"10.64898\/2026.07.29.738916","type":"posted-content","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:05:24Z","timestamp":1785423924000},"source":"Crossref","is-referenced-by-count":0,"title":["Proteomic Profiling Identifies CLDN3 as a Tumor-Selective Therapeutic Target in Small Cell Lung Cancer"],"prefix":"10.64898","author":[{"given":"Brett A.","family":"Schroeder","sequence":"first","affiliation":[{"name":"Developmental Therapeutics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and 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