ArticleMolecular oncology2015
Diphtheria-toxin based anti-human CCR4 immunotoxin for targeting human CCR4(+) cells in vivo.
Article in Molecular oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 38 citations in OpenAlex.
- Therapeutic Promise and Biotechnological Prospects ofInternational journal of molecular sciences · 2025Review
- Development and Characterization of an Anti-PD-L1 Immunotoxin for Targeted Cancer Therapy.Current pharmaceutical biotechnology · 2025Article
- Advances in immunotoxin engineering: precision therapeutic strategies in modern oncology.Medical oncology (Northwood, London, England) · 2024Review
- Review
- Toxicology, pharmacokinetics, and immunogenicity studies of CCR4-IL2 bispecific immunotoxin in rats and minipigs.European journal of pharmacology · 2024Article
- Hosts and Heterologous Expression Strategies of Recombinant Toxins for Therapeutic Purposes.Toxins · 2023Review
- Drug conjugates for targeting regulatory T cells in the tumor microenvironment: guided missiles for cancer treatment.Experimental & molecular medicine · 2023Review
- 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 · 2023Article
- A New Combination: Anti Glypican-3 scFv and Diphtheria Toxin with the Best Flexible Linker.The protein journal · 2022Article
- Bacteria-derived chimeric toxins as potential anticancer agents.Frontiers in oncology · 2022Review
- Tissue Resident Foxp3Frontiers in immunology · 2022Review
- Review
- A novel diphtheria toxin-based bivalent human EGF fusion toxin for treatment of head and neck squamous cell carcinoma.Molecular oncology · 2021Article
- Targeting chemokines for acute lymphoblastic leukemia therapy.Journal of hematology & oncology · 2021Review
- Nonhuman Primate Testing of the Impact of Different Regulatory T Cell Depletion Strategies on Reactivation and Clearance of Latent Simian Immunodeficiency Virus.Journal of virology · 2020Article
- Attenuated diphtheria toxin mediates siRNA delivery.Science advances · 2020Article
- Bispecific human IL2-CCR4 immunotoxin targets human cutaneous T-cell lymphoma.Molecular oncology · 2020Article
- Recent advances with Treg depleting fusion protein toxins for cancer immunotherapy.Immunotherapy · 2019Review
- Targeted Diphtheria Toxin-Based Therapy: A Review Article.Frontiers in microbiology · 2019Review
- Dosing optimization of CCR4 immunotoxin for improved depletion of CCR4Molecular oncology · 2018Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
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-cell acute lymphoblastic leukemia (ALL), adult T-cell 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-toxin based anti-human CCR4 immunotoxins (monovalent, bivalent and single-chain fold-back diabody). Binding analysis by flow cytometry showed that all three versions of the anti-human 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-chain foldback diabody isoform was the strongest among the three versions. In vitro 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-human CCR4 immunotoxin. The single-chain fold-back diabody isoform was 10 fold more potent than its bivalent counterpart and 200 fold more potent than its monovalent counterpart. The in vivo efficacy was assessed using a human CCR4(+) tumor-bearing mouse model. The immunotoxin significantly prolonged the survival of tumor-bearing NOD/SCID IL-2 receptor γ(-/-) (NSG) mice injected with human CCR4(+) acute lymphoblastic leukemia cells compared with the control group. This novel anti-human CCR4 immunotoxin is a promising drug candidate for targeting human CCR4(+) tumor cells and Tregs in vivo.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.