{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T01:08:07Z","timestamp":1790989687171,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2004,2,27]],"date-time":"2004-02-27T00:00:00Z","timestamp":1077840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2004,6,20]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Integrins of the \u03b1v family, such as \u03b1v\u03b23 and \u03b1v\u03b25, are implicated in tumor\u2010induced angiogenesis; but their role in tumor growth has not been fully explored. CNTO 95 is a fully human antibody that recognizes the \u03b1v family of integrins and is likely to be less immunogenic in humans compared to chimeric or humanized antibodies. CNTO 95 bound to purified \u03b1v\u03b23 and \u03b1v\u03b25 with a <jats:italic>K<\/jats:italic><jats:sub>d<\/jats:sub> of approximately 200 pM and to \u03b1v integrin\u2013expressing human cells with a <jats:italic>K<\/jats:italic><jats:sub>d<\/jats:sub> of 1\u201324 nM. <jats:italic>In vitro<\/jats:italic>, CNTO 95 inhibited human melanoma cell adhesion, migration and invasion at doses ranging 7\u201320 nM. In a rat aortic ring sprouting assay, CNTO 95 (approx. 70 nM) completely inhibited sprouting. Using a human melanoma xenograft model in nude mice wherein CNTO 95 recognized \u03b1v\u03b23 and \u03b1v\u03b25 on human tumor cells but not mouse angiogenic integrins, CNTO 95 (10 mg\/kg, 3 times\/week) inhibited growth of human melanoma tumors in nude mice by approximately 80% (<jats:italic>p<\/jats:italic> = 0.0005), suggesting that CNTO 95 inhibited human tumor growth independently of its antiangiogenic activity. In a nude rat human xenograft model where CNTO 95 binds and blocks both tumor and host integrins, this antibody (10 mg\/kg once\/week) reduced final tumor weight by &gt;99% (<jats:italic>p<\/jats:italic> &lt; 0.0001). Based on these preclinical data, a dose\u2010escalating phase I clinical trial in cancer patients has been initiated. To our knowledge, CNTO 95 is the first fully human MAb to \u03b1v integrins that has potent antitumor and antiangiogenic properties in <jats:italic>in vivo<\/jats:italic> preclinical models. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.20116","type":"journal-article","created":{"date-parts":[[2004,3,25]],"date-time":"2004-03-25T16:01:19Z","timestamp":1080230479000},"page":"326-335","source":"Crossref","is-referenced-by-count":138,"title":["CNTO 95, a fully human monoclonal antibody that inhibits \u03b1v integrins, has antitumor and antiangiogenic activity <i>in vivo<\/i>"],"prefix":"10.1002","volume":"110","author":[{"given":"Mohit","family":"Trikha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A.","family":"Nemeth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiming","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia","family":"Sharp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Emmell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill","family":"Giles\u2010Komar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian T.","family":"Nakada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,2,27]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0195-27"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80108-7"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7521539"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0295-149"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00046358"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0277-5379(87)90370-1"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910550305"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9610(97)00168-2"},{"key":"e_1_2_6_10_2","first-page":"401","article-title":"Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma","volume":"143","author":"Weidner N","year":"1993","journal-title":"Am J Pathol"},{"key":"e_1_2_6_11_2","first-page":"419","article-title":"The prognostic significance of tumor vascularity in intermediate\u2010thickness (0.76\u20134.0 mm thick) skin melanoma. 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