None of the other covariates-for example, age, body weight, body mass index, bilirubin, creatinine clearance, disease type (ATL and CTCL), ATL subtype (acute, lymphoma, and chronic), CTCL subtype (mycosis fungoides and Sézary syndrome), CCR4 expression (status or degree), race (Japanese and non-Japanese), renal impairment (normal, mild, moderate, and severe), or performance status-had a statistically significant impact.
This prospective, observational, postmarketing surveillance was conducted to evaluate the safety and effectiveness of mogamulizumab, an anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, in patients with CCR4-positive, relapsed or refractory (r/r) adult T-cell leukemia-lymphoma (ATL) in Japan.
This study suggests that frequencies of CCR4 expression and genomic CCR4 mutations and an association between the two may be considerably different between ATL cases and non-ATL T/NK-cell lymphomas.
The anti-CCR4 mAb, mogamulizumab, offers therapeutic benefit to patients with adult T-cell leukemia-lymphoma (ATL), but skin-related adverse events (AE) such as erythema multiforme occur frequently.
Although the anti-CCR4 antibody mogamulizumab (moga) shows striking antitumor activity against adult T cell leukemia (ATL), it can also cause fatal immunological pathology such as severe skin rash and graft-versus-host disease, which might be attributed to depletion of CCR4<sup>+</sup> regulatory T cells.
IRF4 may represent a therapeutic target in ATL because ATL cells select for a mutant of IRF4 with higher nuclear expression and transcriptional activity, and overexpression of IRF4 induces the expansion of T lymphocytes <i>in vivo</i>.
The Foxp3 expression was similar in ATL and HAMSS, but significantly higher in HAM-SS than AC-SS (p<0.05). p65 was expressed in LSG MNC nuclei from all SS patients and co-expressed with Foxp3.
Mogamulizumab (Mog) is a defucosylated, therapeutic monoclonal antibody, targeting CCR4 and was first approved in Japan for the treatment of adult T-cell leukaemia/lymphoma (ATLL), followed by cutaneous T-cell lymphoma and peripheral T-cell lymphoma.
The present study sought to elucidate the prognosis of adult T-cell leukemia-lymphoma (ATL) patients receiving mogamulizumab, a defucosylated anti-CCR4 monoclonal antibody.
Areas covered: Mogamulizumab is a humanized, defucosylated monoclonal antibody that acts by targeting the CC chemokine receptor 4 (CCR4) on malignant cells of ATL.
Mogamulizumab, an anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, is one of the promising agents for CCR4-positive T-cell lymphomas, especially for ATL.
BAY 1143572-treated ATL-bearing mice (once daily 12.5 mg/kg oral application) demonstrated significantly decreased ATL cell infiltration of the liver and bone marrow, as well as decreased human soluble interleukin-2 receptor levels in serum (reflecting the ATL tumor burden), compared with untreated mice (n = 8 for both).
IL-10-mediated signals act as a switch for lymphoproliferation in Human T-cell leukemia virus type-1 infection by activating the STAT3 and IRF4 pathways.
In this study, by using IL-2-dependent HTLV-1-infected T-cell lines (ILTs) established from patients with ATL and HAM/TSP, we demonstrate that the anti-inflammatory cytokine IL-10 and its downstream signals potentially act as a switch for proliferation in HTLV-1-infected cells.
Galectin-9 as a Predictive Marker for the Onset of Immune-Related Adverse Effects Associated with Anti-CCR4 MoAb Therapy in Patients with Adult T Cell Leukemia.
Transforming activity was further demonstrated by the ability of the FBXW7 D510E mutant to provide IL-2-independent growth of Tax-immortalized human T cells and increase the tumor formation in a xenograft mouse model of ATL.
Mogamulizumab (Mog), a humanized anti-CC chemokine receptor 4 (CCR4) mAb that mediates antibody-dependent cellular cytotoxicity (ADCC) using FcγR IIIa (CD16)-expressing effector cells, has recently been approved for treatment of CCR4-positive adult T-cell leukemia (ATL) in Japan.