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

FEBS Open Bio. 2023 Jul;13(7):1309-1319. doi: 10.1002/2211-5463.13625. Epub 2023 May 15.


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.

Keywords: CCR4-IL2 bispecific immunotoxin; adcetris; brentuximab vedotin; cutaneous T-cell lymphoma; diphtheria toxin; immunotoxin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Immunotoxins* / pharmacology
  • Immunotoxins* / therapeutic use
  • Interleukin-2 / therapeutic use
  • Lymphoma, T-Cell, Cutaneous* / drug therapy
  • Lymphoma, T-Cell, Cutaneous* / pathology
  • Mice
  • Mycosis Fungoides* / drug therapy
  • Mycosis Fungoides* / pathology
  • Sezary Syndrome* / drug therapy
  • Sezary Syndrome* / pathology
  • Skin Neoplasms* / drug therapy
  • Skin Neoplasms* / pathology
  • United States


  • Immunotoxins
  • Interleukin-2
  • Antineoplastic Agents
  • Antibodies, Monoclonal