Depletion of regulatory T cells by targeting CC chemokine receptor type 4 with mogamulizumab

Ni, Xiao; Langridge, Timothy; Duvic, Madeleine

doi:10.1080/2162402x.2015.1011524

Cited by 32 publications

(20 citation statements)

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“…A similar response rate of 29% (2/7), all partial, was observed in a phase II Japanese study. 254,255 In addition to ADCC-mediated clearance of malignant T cells, mogamulizumab may inhibit T reg -mediate immune suppression, 256,257 and may warrant further investigation with immunomodulatory therapies, including immune checkpoint blockade. 258 151,153,263 are infrequently durable, 148,149 and frequently associated with significant myelosuppression and infectious complications.…”

Section: Monoclonal Antibodies and Immunotoxinsmentioning

confidence: 99%

Cutaneous T‐cell lymphoma: 2017 update on diagnosis, risk‐stratification, and management

Wilcox

2017

American J Hematol

111

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Section: Monoclonal Antibodies and Immunotoxinsmentioning

confidence: 99%

Cutaneous T‐cell lymphoma: 2017 update on diagnosis, risk‐stratification, and management

Wilcox

2017

American J Hematol

111

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“…By strongly activating NK cells, mogamulizumab can induce NK cells to release cytokines and related cytotoxic molecules which might be the mechanism of infusion reaction [15,28,29]. Mogamulizumab can reduce the level of CCR4-positive malignant T cells locally and systematically, and can also eliminate CCR4-positive Tregs leading to Tregs depletion, which contributes to the enhancement of antitumor effects and the immunotherapeutic effect of activating the host immune response [18,30]. However, mogamulizumab induced Tregs depletion can cause alteration of the immune balance, which may unleash various undesirable infections [22,31].…”

Section: Discussionmentioning

confidence: 99%

Safety and efficacy profile of mogamulizumab (Poteligeo) in the treatment of cancers: An update evidence from 14 studies 

Zhang

Sun

et al. 2020

Preprint

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Background: CC chemokine receptor 4 (CCR4), the receptor for CCL22 and CCL17, is expressed on the surface of effector Tregs that have the highest suppressive effects on antitumor immune response. CCR4 is also widely expressed on the surface of tumor cells from patients with adult T-cell leukemia/lymphoma (ATL), peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL). Mogamulizumab is a humanized, IgG1 kappa monoclonal antibody that is directed against CCR4. By reducing the number of CCR4-positive Tregs and tumor cells, the mogamulizumab can reduce tumor burden and boost antitumor immunity to achieve antitumor effects.Methods: We examined the PubMed and ClinicalTrials.gov until 1 February 2020. Considering variability in different studies, we selected the adverse events (AEs), overall survival (OS), progression‐free survival (PFS), objective responses rate (ORR) and Hazard Ratio (HR) for PFS to evaluate the safety and efficacy profile of mogamulizumab. Results: When patients were treated with mogamulizumab monotherapy, the most common all-grade AEs were lymphopenia, infusion reaction, fever, rash and chills while the most common grade ≥3 AEs were lymphopenia, neutropenia and rash. When patients were treated with combined therapy of mogamulizumab and other drugs, the most common all-grade AEs were neutropenia, anaemia, lymphopenia and gastrointestinal disorder, while the most common grade ≥3 AEs was lymphopenia. For patients treated with mogamulizumab monotherapy, the pooled ORR and mean PFS were 0.430 (95% CI: 0.393-0.469) and 1.060 months (95% CI: 1.043-1.077), respectively. For patients treated with combined therapy of mogamulizumab and other drugs, the pooled ORR was 0.203 (95% CI: 0.022-0.746) while the pooled PFS and OS were 2.093 months (95% CI: 1.602-2.584) and 6.591 months (95% CI: 6.014-7.167), respectively.Conclusions: Based on present evidence, we believed that mogamulizumab had clinically meaningful antitumor activity with acceptable toxicity which is a novel therapy in treating patients with cancers.

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“…Further research should be performed, especially that in some diseases knowledge on the Tregs status may be nowadays, the basis of new successful treatments which modulate the Tregs number and function. For example, mogamulizumab (KW-671) is a new defucosylated anti-CCR4 monoclonal antibody which reduces the numbers of CCR4 + malignant T cells and CCR4 + Treg cells in cutaneous T cell lymphoma [ 142 ]. New strategies based on ex vivo proliferation and transplantation of autologous Tregs in autoimmune and allergic diseases have been recently developed [ 143 ].…”

Section: Tregs In Mastocytosismentioning

confidence: 99%

The role of regulatory T cells and genes involved in their differentiation in pathogenesis of selected inflammatory and neoplastic skin diseases. Part II: The Treg role in skin diseases pathogenesis

Nedoszytko

Lange

Sokołowska‐Wojdyło

et al. 2017

pdia

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Regulatory FOXP3+ T cells (Tregs) constitute 5% to 10% of T cells in the normal human skin. They play an important role in the induction and maintenance of immunological tolerance. The suppressive effects of these cells are exerted by various mechanisms including the direct cytotoxic effect, anti-inflammatory cytokines, metabolic disruption, and modulation of the dendritic cells function. The deficiency of Treg cells number or function are one of the basic elements of the pathogenesis of many skin diseases, such as psoriasis, atopic dermatitis, bacterial and viral infections. They also play a role in the pathogenesis of T cell lymphomas of the skin (cutaneous T cell lymphomas – CTCL), skin tumors and mastocytosis. Here, in the second part of the cycle, we describe dysfunctions of Tregs in selected skin diseases.

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Depletion of regulatory T cells by targeting CC chemokine receptor type 4 with mogamulizumab

Cited by 32 publications

References 10 publications

Cutaneous T‐cell lymphoma: 2017 update on diagnosis, risk‐stratification, and management

Cutaneous T‐cell lymphoma: 2017 update on diagnosis, risk‐stratification, and management

Safety and efficacy profile of mogamulizumab (Poteligeo) in the treatment of cancers: An update evidence from 14 studies

The role of regulatory T cells and genes involved in their differentiation in pathogenesis of selected inflammatory and neoplastic skin diseases. Part II: The Treg role in skin diseases pathogenesis

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Depletion of regulatory T cells by targeting CC chemokine receptor type 4 with mogamulizumab

Cited by 32 publications

References 10 publications

Cutaneous T‐cell lymphoma: 2017 update on diagnosis, risk‐stratification, and management

Cutaneous T‐cell lymphoma: 2017 update on diagnosis, risk‐stratification, and management

Safety and efficacy profile of mogamulizumab (Poteligeo) in the treatment of cancers: An update evidence from 14 studies&nbsp;

The role of regulatory T cells and genes involved in their differentiation in pathogenesis of selected inflammatory and neoplastic skin diseases. Part II: The Treg role in skin diseases pathogenesis

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Safety and efficacy profile of mogamulizumab (Poteligeo) in the treatment of cancers: An update evidence from 14 studies