{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T14:56:11Z","timestamp":1772117771006,"version":"3.50.1"},"reference-count":26,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T00:00:00Z","timestamp":1684108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R42CA261547\u201001"],"award-info":[{"award-number":["1R42CA261547\u201001"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01HL152405"],"award-info":[{"award-number":["U01HL152405"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:p>\n                    Cutaneous T\u2010cell lymphoma (CTCL) encompasses two main subtypes: mycosis fungoides and Sezary syndrome. Global response rates for the systemic treatment of mycosis fungoides and Sezary syndrome are approximately 30%, and none of these treatments are thought to be curative. C\u2013C chemokine receptor type 4 (CCR4) and CD25 are encouraging targets for the treatment of CTCL and are individually targeted by mogamulizumab and denileukin diftitox, respectively. We developed a novel CCR4\u2010IL2 bispecific immunotoxin (CCR4\u2010IL2 IT) targeting both CCR4 and CD25. CCR4\u2010IL2 IT demonstrated superior efficacy against CCR4\n                    <jats:sup>+<\/jats:sup>\n                    CD25\n                    <jats:sup>+<\/jats:sup>\n                    CD30\n                    <jats:sup>+<\/jats:sup>\n                    CTCL in an immunodeficient\n                    <jats:italic>NSG<\/jats:italic>\n                    mouse tumor model. Investigative New Drug\u2010enabling studies of CCR4\u2013IL2 IT are ongoing, including Good Manufacturing Practice production and toxicology studies. In this study, we compared the\n                    <jats:italic>in\u2009vivo<\/jats:italic>\n                    efficacy of CCR4\u2010IL2 IT versus the US Food and Drug Administration\u2013approved drug, brentuximab, using an immunodeficient mouse CTCL model. We demonstrated that CCR4\u2013IL2 IT was significantly more effective in prolonging survival than brentuximab, and combination treatment of CCR4\u2013IL2 IT and brentuximab was more effective than brentuximab or CCR4\u2013IL2 IT alone in an immunodeficient NSG mouse CTCL model. Thus, CCR4\u2013IL2 IT is a promising novel therapeutic drug candidate for CTCL treatment.\n                  <\/jats:p>","DOI":"10.1002\/2211-5463.13625","type":"journal-article","created":{"date-parts":[[2023,5,9]],"date-time":"2023-05-09T01:05:15Z","timestamp":1683594315000},"page":"1309-1319","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["<scp>CCR4\u2010IL2<\/scp>\n                    bispecific immunotoxin is more effective than brentuximab for targeted therapy of cutaneous T\u2010cell lymphoma in a mouse\n                    <scp>CTCL<\/scp>\n                    model"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9035-3867","authenticated-orcid":false,"given":"Zhaohui","family":"Wang","sequence":"first","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine University of Colorado Anschutz Medical Campus  Aurora CO USA"},{"name":"Division of Transplant Surgery, Department of Surgery, School of Medicine University of Colorado Anschutz Medical Campus  Aurora CO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jihong","family":"Ma","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine University of Colorado Anschutz Medical Campus  Aurora CO USA"},{"name":"Division of Transplant Surgery, Department of Surgery, School of Medicine University of Colorado Anschutz Medical Campus  Aurora CO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huiping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine University of Colorado Anschutz Medical Campus  Aurora CO USA"},{"name":"Division of Transplant Surgery, Department of Surgery, School of Medicine University of Colorado Anschutz Medical Campus  Aurora CO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rashmi","family":"Ramakrishna","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine University of Colorado Anschutz Medical Campus  Aurora CO USA"},{"name":"Division of Transplant Surgery, Department of Surgery, School of Medicine University of Colorado Anschutz Medical Campus  Aurora CO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle","family":"Mintzlaff","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine University of Colorado Anschutz Medical Campus  Aurora CO USA"},{"name":"Division of Transplant Surgery, Department of Surgery, School of Medicine University of Colorado Anschutz Medical Campus  Aurora CO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David W.","family":"Mathes","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine University of Colorado Anschutz Medical Campus  Aurora CO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth A.","family":"Pomfret","sequence":"additional","affiliation":[{"name":"Division of Transplant Surgery, Department of Surgery, School of Medicine University of Colorado Anschutz Medical Campus  Aurora CO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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