{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T22:46:24Z","timestamp":1778625984937,"version":"3.51.4"},"reference-count":24,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2015,4,25]],"date-time":"2015-04-25T00:00:00Z","timestamp":1429920000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:p>CC chemokine receptor 4 (CCR4) has attracted much attention as a promising therapeutic drug target for CCR4+ tumor cells and Tregs. CCR4 is expressed on some tumor cells such as T\u2010cell acute lymphoblastic leukemia (ALL), adult T\u2010cell leukemia\/lymphoma (ATLL), adult peripheral T cell lymphoma (PTCL) and cutaneous T cell lymphoma (CTCL). CCR4 is also expressed on majority of Tregs, mainly effector Tregs. In this study we have successfully developed three versions of diphtheria\u2010toxin based anti\u2010human CCR4 immunotoxins (monovalent, bivalent and single\u2010chain fold\u2010back diabody). Binding analysis by flow cytometry showed that all three versions of the anti\u2010human CCR4 immunotoxins bound to the human CCR4+ tumor cell line as well as CCR4+ human PBMC. The bivalent isoform bound stronger than its monovalent counterpart and the single\u2010chain foldback diabody isoform was the strongest among the three versions. In\u00a0vitro efficacy analysis demonstrated that the bivalent isoform was 20 fold more potent in inhibiting cellular proliferation and protein synthesis in human CCR4+ tumor cells compared to the monovalent anti\u2010human CCR4 immunotoxin. The single\u2010chain fold\u2010back diabody isoform was 10 fold more potent than its bivalent counterpart and 200 fold more potent than its monovalent counterpart. The in\u00a0vivo efficacy was assessed using a human CCR4+ tumor\u2010bearing mouse model. The immunotoxin significantly prolonged the survival of tumor\u2010bearing NOD\/SCID IL\u20102 receptor \u03b3\u2212\/\u2212 (NSG) mice injected with human CCR4+ acute lymphoblastic leukemia cells compared with the control group. This novel anti\u2010human CCR4 immunotoxin is a promising drug candidate for targeting human CCR4+ tumor cells and Tregs in\u00a0vivo.<\/jats:p>","DOI":"10.1016\/j.molonc.2015.04.004","type":"journal-article","created":{"date-parts":[[2015,4,26]],"date-time":"2015-04-26T04:56:36Z","timestamp":1430024196000},"page":"1458-1470","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Diphtheria\u2010toxin based anti\u2010human CCR4 immunotoxin for targeting human CCR4+ cells 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