Mogamulizumab for the treatment of relapsed or refractory adult T-cell leukemia-lymphoma

Winsett, Frank; Lewis, Daniel; Duvic, Madeleine

doi:10.1080/17474086.2017.1361819

Cited by 6 publications

(3 citation statements)

References 23 publications

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“…Furthermore, a multi-center phase III study of mogamulizumab versus vorinostat, a histone deacetylase inhibitor, has been initiated in patients with CCR4-positive cutaneous T-cell lymphoma. Finally, a multi-center phase Ib trial examining a combination treatment consisting of mogamulizumab and utomilumab, a 4-1BB agonist, for the treatment of advanced solid tumors was started ( Identifier: NCT02444793) [ 113 ]. Mechanistically, mogamulizumab is thought to also target CCR4-positive Treg cells and thereby facilitate antitumor immunity.…”

Section: Therapeutic Targeting Of Ccl17/ccl22 and Ccr4mentioning

confidence: 99%

“…Mechanistically, mogamulizumab is thought to also target CCR4-positive Treg cells and thereby facilitate antitumor immunity. However, this inhibition of Treg cellular functions can result in severe adverse effects affecting the skin, underscoring the inherent risks of altering Treg cell biology [ 113 ]. Taking a ligand-sided approach, Abboud and colleagues (2015) have identified decoy molecules for CCL17 and CCL22, termed neutraligands, with anti-inflammatory activity.…”

Section: Therapeutic Targeting Of Ccl17/ccl22 and Ccr4mentioning

confidence: 99%

See 1 more Smart Citation

The C-C Chemokines CCL17 and CCL22 and Their Receptor CCR4 in CNS Autoimmunity

Scheu

Ali

Ruland

et al. 2017

IJMS

115

105

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Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). It affects more than two million people worldwide, mainly young adults, and may lead to progressive neurological disability. Chemokines and their receptors have been shown to play critical roles in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a murine disease model induced by active immunization with myelin proteins or transfer of encephalitogenic CD4+ T cells that recapitulates clinical and neuropathological features of MS. Chemokine ligand-receptor interactions orchestrate leukocyte trafficking and influence multiple pathophysiological cellular processes, including antigen presentation and cytokine production by dendritic cells (DCs). The C-C class chemokines 17 (CCL17) and 22 (CCL22) and their C-C chemokine receptor 4 (CCR4) have been shown to play an important role in homeostasis and inflammatory responses. Here, we provide an overview of the involvement of CCR4 and its ligands in CNS autoimmunity. We review key clinical studies of MS together with experimental studies in animals that have demonstrated functional roles of CCR4, CCL17, and CCL22 in EAE pathogenesis. Finally, we discuss the therapeutic potential of newly developed CCR4 antagonists and a humanized anti-CCR4 antibody for treatment of MS.

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Section: Therapeutic Targeting Of Ccl17/ccl22 and Ccr4mentioning

confidence: 99%

Section: Therapeutic Targeting Of Ccl17/ccl22 and Ccr4mentioning

confidence: 99%

The C-C Chemokines CCL17 and CCL22 and Their Receptor CCR4 in CNS Autoimmunity

Scheu

Ali

Ruland

et al. 2017

IJMS

115

105

View full text Add to dashboard Cite

show abstract

“…In the same fashion, as in ADCP mechanism of action, natural killer cells (NK cells), PBMC, (peripheral blood monocytes cells), complements (serum) plays a significant roles in antibodydependent cellular cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC) therapeutic activities. Recently, mogamulizumab anti-CC chemokine receptor 4 (CCR4) antibody has shown significant ADCC based therapeutic efficacy in treating Adult T cell Lymphoma-Leukemia in Japan [73].…”

Section: Antibody Mechanism Of Action Against Leukemia and Lymphoma Tmentioning

confidence: 99%

Development of Therapeutic Antibody Technology And Recent Perspectives For Leukemia-Lymphoma Treatment

Yirga¹,

Lin²,

Huang³

et al. 2019

J Leuk

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Advancement of monoclonal antibodies (Mabs) to be accepted as a therapy has long history. This article describes the dramatic developmental trend of therapeutic antibody technology and their significant role for treatment of leukemia-lymphoma at the current time. The therapeutic Mab technology development from murine (mouse origin) to fully human resulted in low immunogenicity and high quality Mabs. Chemotherapy is standard care for leukemialymphoma treatments. However, it is associated with high toxicities (side effects), painful and relatively ineffective against certain leukemia-lymphoma subtypes. The remarkable contribution of Von Behring, Paul Ehrlich and the discovery of hybridoma technology marked the beginning of antibodies for therapeutic applications. Rituximab is the first Mab approved by Food and Drug Administration against B-cell malignancies. Today, a number of effective Mabs targeting leukemia and lymphoma were approved and successfully developed. The Mab therapeutic phenomena in the body (also called war in the blood) has various mechanism of actions. In recent years, Mab against leukemialymphoma achieved significantly therapeutic outcomes, eventually this led to traditional chemotherapy treatment free era. We also reviewed that, the therapeutic efficacy of Mabs against leukemia-lymphoma as compared antibody alone and antibody conjugated with potent chemotherapy or cytotoxic drugs. This article extends our understanding of advancements in therapeutic Mabs technology and provides new insights of Mab leukemia-lymphomas therapy. We also encourage further more studies for Mab based diagnostics, treatments of leukemia and lymphomas.

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Monoclonal Antibody and Targeted Toxin Therapy

Bast¹,

Zalutsky²

2022

Holland‐Frei Cancer Medicine

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Overview Monoclonal antibodies have impacted significantly on the care of patients with cancer. Overall, the US FDA has approved 100 different monoclonal antibodies for the treatment of human diseases. More than 40 monoclonal antibodies, cytotoxic drug conjugates, radionuclide conjugates, and targeted toxins have been approved for the treatment of more than two dozen different malignancies. Useful monoclonal antibodies have most frequently targeted structural proteins and receptors on the cancer cell surface (CD20 by rituximab, HER2 by trastuzumab, and pertuzumab), inhibiting growth, inducing apoptosis, and enhancing chemotherapy, but some have targeted cytokines (IL‐6 by siltuximab), growth factors (vascular endothelial growth factor (VEGF) by bevacizumab), and growth factor receptors (VEGFR2 by ramucirumab) that affect both cancer cells and normal stromal cells including endothelial cells and lymphocytes. Monoclonal antibodies have disrupted checkpoint inhibition of effector T lymphocytes by blocking CTLA4 (ipilimumab), PD1 (pembrolizumab, nivolumab, and cemiplimab), and PD‐L1 (atezolizumab, durvalumab, and avelumab). In the case of trastuzumab and pertuzumab, binding of the two antibodies to different sites on the HER2 cell surface receptor has produced greater antitumor activity than either alone. Enhanced cancer cell killing has also been achieved by conjugation of antibodies with cytotoxic drugs (emtansine to anti‐HER2 trastuzumab and vedotin to anti‐CD30 brentuximab) or radionuclide conjugates ( 90 Y to anti‐CD20 ibritumomab tiuxetan) permitting effective treatment of patients who had failed therapy with unconjugated antibodies. There are several barriers to effective therapy with monoclonal antibodies including antigen specificity, antigenic modulation, heterogeneity of antigen expression, effective delivery of antibodies to cancer cells, potency of effector mechanisms, and response to immunologically foreign globulin. The latter problem has been circumvented with the use of chimeric constructs, humanization of murine antibodies, and developing genetically engineered mice with the ability to develop fully human antibodies. Use of unconjugated antibodies is likely to improve as our knowledge of tumor biology and immunology grows, identifying targets such as OX‐40 ligand. Use of smaller molecularly engineered binding constructs may improve pharmacokinetics and pharmacodynamics of monoclonal antibody and conjugate therapy. Combinations of antibodies may be required to compensate for antigenic heterogeneity. Development of more effective antibody–drug conjugates will require the identification of monoclonal reagents that target tumor‐initiating stem cells. Use of antibody fragments, pretargeting, and the use of alpha‐emitters are promising approaches to improving antibody–radionuclide conjugates. Development of targeted toxins must be further explored.

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Mogamulizumab for the treatment of relapsed or refractory adult T-cell leukemia-lymphoma

Cited by 6 publications

References 23 publications

The C-C Chemokines CCL17 and CCL22 and Their Receptor CCR4 in CNS Autoimmunity

The C-C Chemokines CCL17 and CCL22 and Their Receptor CCR4 in CNS Autoimmunity

Development of Therapeutic Antibody Technology And Recent Perspectives For Leukemia-Lymphoma Treatment

Monoclonal Antibody and Targeted Toxin Therapy

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