By enhancing antibody-dependent cellular cytotoxicity, mogamulizumab selectively depletes CCR4-positive malignant lymphocytes and has demonstrated significant clinical activity in advanced CTCL, including in patients refractory to multiple prior therapies. [...].
P2, N=23, Recruiting, University of Michigan Rogel Cancer Center | Trial completion date: Apr 2027 --> Dec 2027 | Trial primary completion date: Apr 2026 --> Dec 2026
12 days ago
Trial completion date • Trial primary completion date
Despite the use of antiviral therapies and targeted monoclonal antibodies, therapeutic failure is common due to genomic instability-specifically TP53 mutations compromising Zidovudine/Interferon efficacy and CCR4 antigenic variations leading to mogamulizumab resistance. This review delineates the multi-step journey of HTLV-1-driven clonal evolution and evaluates the molecular barriers to effective clinical management.
In this article, we discuss the clinical and histopathologic findings of cutaneous adverse reactions to newer medications, including those recently approved to treat inflammatory skin diseases, such as dupilumab for atopic dermatitis and IL-12/-23 and IL-23 specific inhibitors for psoriasis, as well as those with oncologic indications, including immune checkpoint inhibitors, mogamulizumab, and enfortumab vedotin.
This is the first documented case of BKPyV-associated PML in a Mogamulizumab-treated patient. These findings highlight intra-host heterogeneity at the protein level, possibly reflecting compartment-specific viral evolution, and underscore the need for vigilant BKPyV and JCPyV monitoring during Mogamulizumab treatment.
The observed median overall survival (OS) was 11.5 months, with 1 reported death due to septic shock in a patient who underwent salvage allo-HSCT after mogamulizumab failure. The results of this study reaffirm the efficacy of Mogamulizumab therapy for patients with Mycosis Fungoides and Sézary Syndrome in a real-world setting, which involves treatment decisions that must often consider patient heterogeneity, comorbidities, and prior lines of therapy.
Therapeutically, agents targeting chemokine pathways, most notably the CCR4 monoclonal antibody Mogamulizumab, have demonstrated clinical efficacy, while emerging inhibitors of CCR6, CCR5, and CXCR4 offer promising avenues for intervention. We further highlight how recent single-cell and other high-dimensional omics studies refine cell-type-specific chemokine sources and receptor expression, enabling more precise mapping of chemokine-driven intercellular communication programs in CTCL TME remodeling and better prioritization of therapeutic targets and biomarkers.
P2, N=23, Recruiting, University of Michigan Rogel Cancer Center | Trial completion date: Dec 2026 --> Apr 2027 | Trial primary completion date: Dec 2025 --> Apr 2026
4 months ago
Trial completion date • Trial primary completion date
XL-11 mediates potent antitumor immunity in advanced HER2+ tumors while avoiding reducing Tregs throughout the body. XL-11 also acts synergistically with anti-PD-1 therapy, and exhibits favorable stability and PK supporting clinical translation. This work advances Treg-targeted therapies in HER2+ tumors and overcomes the therapeutic limitations of mogamulizumab.
5 months ago
Journal
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PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • CCR4 (C-C Motif Chemokine Receptor 4)
Tregs were increased and activated in DTC tumor tissue, indicating that they play an important role in creating an immunosuppressive microenvironment in DTC. The results suggest that eTreg-depletion immunotherapy using an anti-CCR4 antibody (mogamulizumab) might be effective for treating DTC.