{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T02:56:50Z","timestamp":1792119410238,"version":"4.4.0"},"reference-count":53,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,12,3]],"date-time":"2019-12-03T00:00:00Z","timestamp":1575331200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:p>\n                    cMet is a well\u2010characterized oncogene that is the target of many drugs including small molecule and biologic pathway inhibitors, and, more recently,\u00a0antibody\u2013drug conjugates (ADCs). However, the clinical benefit from cMet\u2010targeted therapy has been limited. We developed a novel cMet\u2010targeted \u2018third\u2010generation\u2019 ADC, TR1801\u2010ADC, that was optimized at different levels including specificity, stability, toxin\u2013linker, conjugation site, and\n                    <jats:italic>in\u00a0vivo<\/jats:italic>\n                    efficacy. Our nonagonistic cMet antibody was site\u2010specifically conjugated to the pyrrolobenzodiazepine (PBD) toxin\u2013linker tesirine and has picomolar activity in cancer cell lines derived from different solid tumors including lung, colorectal, and gastric cancers. The potency of our cMet ADC is independent of MET gene copy number, and its antitumor activity was high not only in high cMet\u2010expressing cell lines but also in medium\u2010to\u2010low cMet cell lines (40\u00a0000\u201390\u00a0000 cMet\/cell) in which a cMet ADC with tubulin inhibitor payload was considerably less potent.\n                    <jats:italic>In\u00a0vivo<\/jats:italic>\n                    xenografts with low\u2013medium cMet expression were also very responsive to TR1801\u2010ADC at a single dose, while a cMet ADC using a tubulin inhibitor showed a substantially reduced efficacy. Furthermore, TR1801\u2010ADC had excellent efficacy with significant antitumor activity in 90% of tested patient\u2010derived xenograft models of gastric, colorectal, and head and neck cancers: 7 of 10 gastric models, 4 of 10 colorectal cancer models, and 3 of 10 head and neck cancer models showed complete tumor regression after a single\u2010dose administration. Altogether, TR1801\u2010ADC is a new generation cMet ADC with best\u2010in\u2010class preclinical efficacy and good tolerability in rats.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.12600","type":"journal-article","created":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T04:19:33Z","timestamp":1574050773000},"page":"54-68","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["TR1801\u2010ADC: a highly potent cMet antibody\u2013drug conjugate with high activity in patient\u2010derived xenograft models of solid tumors"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6885-5951","authenticated-orcid":false,"given":"Marco","family":"Gymnopoulos","sequence":"first","affiliation":[{"name":"Tanabe Research Laboratories U.S.A., Inc. 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