ArticleMolecular cancer therapeutics2012
Humanization of an anti-CCR4 antibody that kills cutaneous T-cell lymphoma cells and abrogates suppression by T-regulatory cells.
Article in Molecular cancer therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 72 citations in OpenAlex.
- Targeting Metabolic Pathways to Direct T-Cell Trafficking: Therapeutic Perspectives.Biomedicines · 2026Review
- Spatial ecotype in tumor immune exclusion: from spatial architecture to therapeutic strategies.Molecular cancer · 2026Review
- CAR T cells targeting CCR4 selectively deplete human Tregs ex vivo and in vivo.Blood advances · 2026Article
- Review
- Downstream STING pathways IRF3 and NF-κB differentially regulate CCL22 in response to cytosolic dsDNA.Cancer gene therapy · 2024Article
- Drug conjugates for targeting regulatory T cells in the tumor microenvironment: guided missiles for cancer treatment.Experimental & molecular medicine · 2023Review
- Identifying highly active anti-CCR4 CAR T cells for the treatment of T-cell lymphoma.Blood advances · 2023Article
- Radiation for hematologic malignancies: from cell killing to immune cell priming.Frontiers in oncology · 2023Review
- Cancer Resistance to Immunotherapy: Molecular Mechanisms and Tackling Strategies.International journal of molecular sciences · 2022Review
- Deconvolution of Adult T-Cell Leukemia/Lymphoma With Single-Cell RNA-Seq Using Frozen Archived Skin Tissue Reveals New Subset of Cancer-Associated Fibroblast.Frontiers in immunology · 2022Article
- The immunopathogenesis and immunotherapy of cutaneous T cell lymphoma: Pathways and targets for immune restoration and tumor eradication.Journal of the American Academy of Dermatology · 2021Review
- The Neutrophil: The Underdog That Packs a Punch in the Fight against Cancer.International journal of molecular sciences · 2020Review
- Targeted Diphtheria Toxin-Based Therapy: A Review Article.Frontiers in microbiology · 2019Review
- Bexarotene Reduces Production of CCL22 From Tumor-Associated Macrophages in Cutaneous T-Cell Lymphoma.Frontiers in oncology · 2019Article
- RNA Aptamers Recognizing Murine CCL17 Inhibit T Cell Chemotaxis and Reduce Contact Hypersensitivity In Vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- Opportunities for therapeutic antibodies directed at G-protein-coupled receptors.Nature reviews. Drug discovery · 2017Review
- Chimeric antigen receptor modified T cells that target chemokine receptor CCR4 as a therapeutic modality for T-cell malignancies.American journal of hematology · 2017Article
- Drug discovery and therapeutic delivery for the treatment of B and T cell tumors.Advanced drug delivery reviews · 2017Review
- Review
- Cancer Immunotherapy: Historical Perspective of a Clinical Revolution and Emerging Preclinical Animal Models.Frontiers in immunology · 2017Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of neoplastic disorders characterized by clonally derived and skin-homing malignant T cells that express high level of chemokine receptor CCR4, which is associated with their skin-homing capacity. CCR4 is also highly expressed on T-regulatory cells (Tregs) that can migrate to several different types of chemotactic ligand CCL17- and CCL22-secreting tumors to facilitate tumor cell evasion from immune surveillance. Thus, its high-level expression on CTCL cells and Tregs makes CCR4 a potential ideal target for antibody-based immunotherapy for CTCL and other types of solid tumors. Here, we conducted humanization and affinity optimization of a murine anti-CCR4 monoclonal antibody (mAb), mAb1567, that recognizes both the N-terminal and extracellular domains of CCR4 with high affinity and inhibits chemotaxis of CCR4(+) CTCL cells. In a mouse CTCL tumor model, mAb1567 exhibited a potent antitumor effect and in vitro mechanistic studies showed that both complement-dependent cytotoxicity (CDC) and neutrophil-mediated antibody-dependent cellular cytotoxicity (ADCC) likely mediated this effect. mAb1567 also exerts human NK cell-mediated ADCC activity in vitro. Moreover, mAb1567 also effectively inhibits chemotaxis of CD4(+)CD25(high) Tregs via CCL22 and abrogates Treg suppression activity in vitro. An affinity-optimized variant of humanized mAb1567, mAb2-3, was selected for further preclinical development based on its higher binding affinity and more potent ADCC and CDC activities. Taken together, this high-affinity humanized mAb2-3 with potent antitumor effect and a broad range of mechanisms of action may provide a novel immunotherapy for CTCL and other solid tumors.
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Registered trials
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.