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Bispecific human IL2-CCR4 immunotoxin targets human cutaneous T-cell lymphoma.


ABSTRACT: The majority of clinically diagnosed cutaneous T-cell lymphomas (CTCL) highly express the cell-surface markers CC chemokine receptor 4 (CCR4) and/or CD25. Recently, we have developed diphtheria toxin-based recombinant Ontak®-like human IL2 fusion toxin (IL2 fusion toxin) and anti-human CCR4 immunotoxin (CCR4 IT). In this study, we first compared the efficacy of the CCR4 IT vs IL2 fusion toxin for targeting human CD25+ CCR4+ CTCL. We demonstrated that CCR4 IT was more effective than IL2 fusion toxin. We further constructed an IL2-CCR4 bispecific IT. The bispecific IT was significantly more effective than either IL2 fusion toxin or CCR4 IT alone. The bispecific IT is a promising novel targeted therapeutic drug candidate for the treatment of refractory and recurrent human CD25+ and/or CCR4+ CTCL.

SUBMITTER: Wang H 

PROVIDER: S-EPMC7191189 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Bispecific human IL2-CCR4 immunotoxin targets human cutaneous T-cell lymphoma.

Wang Haoyu H   Wang Zhaohui Z   Zhang Huiping H   Qi Zeng Z   Johnson Ariel C AC   Mathes David D   Pomfret Elizabeth A EA   Rubin Erin E   Huang Christene A CA   Wang Zhirui Z  

Molecular oncology 20200313 5


The majority of clinically diagnosed cutaneous T-cell lymphomas (CTCL) highly express the cell-surface markers CC chemokine receptor 4 (CCR4) and/or CD25. Recently, we have developed diphtheria toxin-based recombinant Ontak®-like human IL2 fusion toxin (IL2 fusion toxin) and anti-human CCR4 immunotoxin (CCR4 IT). In this study, we first compared the efficacy of the CCR4 IT vs IL2 fusion toxin for targeting human CD25<sup>+</sup> CCR4<sup>+</sup> CTCL. We demonstrated that CCR4 IT was more effect  ...[more]

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