CCR4-IL2 bispecific immunotoxin is more effective than brentuximab for targeted therapy of cutaneous T-cell lymphoma in a mouse CTCL model.

Autor:	Wang Z; Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Division of Transplant Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Ma J; Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Division of Transplant Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Zhang H; Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Division of Transplant Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Ramakrishna R; Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Division of Transplant Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Mintzlaff D; Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Division of Transplant Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Mathes DW; Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Pomfret EA; Division of Transplant Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Lucia MS; Department of Pathology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Gao D; Department of Pediatrics, University of Colorado Cancer Center Biostatistics and Bioinformatics Shared Resource, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Haverkos BM; University of Colorado Hospital, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Wang Z; Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Division of Transplant Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Jazyk:	angličtina
Zdroj:	FEBS open bio [FEBS Open Bio] 2023 Jul; Vol. 13 (7), pp. 1309-1319. Date of Electronic Publication: 2023 May 15.
DOI:	10.1002/2211-5463.13625
Abstrakt:	Cutaneous T-cell 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-C 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-IL2 bispecific immunotoxin (CCR4-IL2 IT) targeting both CCR4 and CD25. CCR4-IL2 IT demonstrated superior efficacy against CCR4 + CD25 + CD30 + CTCL in an immunodeficient NSG mouse tumor model. Investigative New Drug-enabling studies of CCR4-IL2 IT are ongoing, including Good Manufacturing Practice production and toxicology studies. In this study, we compared the in vivo efficacy of CCR4-IL2 IT versus the US Food and Drug Administration-approved drug, brentuximab, using an immunodeficient mouse CTCL model. We demonstrated that CCR4-IL2 IT was significantly more effective in prolonging survival than brentuximab, and combination treatment of CCR4-IL2 IT and brentuximab was more effective than brentuximab or CCR4-IL2 IT alone in an immunodeficient NSG mouse CTCL model. Thus, CCR4-IL2 IT is a promising novel therapeutic drug candidate for CTCL treatment. (© 2023 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
Databáze:	MEDLINE
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