Mogamulizumab for the treatment of cutaneous T-cell lymphoma: recent advances and clinical potential

Duvic, Madeleine; Evans, Mark; Wang, Casey

doi:10.1177/2040620716636541

Cited by 42 publications

(34 citation statements)

References 19 publications

(24 reference statements)

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“…Afucosylated antibody glycoforms uniquely exhibit enhanced Fc engagement with the activatory FcγRIIIa and FcγRIIIb resulting in more potent ADCC and ADCP [56][57][58] . Since the first definitive report of defucosylation-mediated ADCC enhancement in the early 2000s 44 , two glyco-engineered, afucosylated, mAbs have already been approved for cancer therapies [86][87] . A list of fucose-engineered antibodies developed for clinical oncology are shown in Table 1.…”

Section: Glyco-engineered Antibodies In Clinical Oncologymentioning

confidence: 99%

“…Generated through the Potelligent technology, it is an afucosylated therapeutic targeting the chemokine receptor CCR4. CCR4 is normally expressed on CD4+ Th2 cells and some other T cell subsets but is also abundant on most adult T cell leukaemia lymphoma (ATLL) and cutaneous T-cell lymphomas (CTCL) 86,90 . Mogamulizumab gained approval in 2012 for treatment of relapsed or refractory CCR4+ ATLL, and later in 2014 for treatment of relapsed or refractory CCR4+ CTCL 86 .…”

Section: Mogamulizumab the First Approved Glyco-engineered Mabmentioning

confidence: 99%

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Improving Antibody-Based Cancer Therapeutics Through Glycan Engineering

Marshall

Cragg

et al. 2017

BioDrugs

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Antibody-based therapeutics has emerged as a major tool in cancer treatment. Guided by the superb specificity of the antibody variable domain, it allows the precise targeting of tumour markers. Recently, eliciting cellular effector functions, mediated by the Fc domain, has gained traction as a means by which to generate more potent antibody therapeutics. Extensive mutagenesis studies of the Fc protein backbone has enabled the generation of Fc variants that more optimally engage the Fcγ receptors known to mediate cellular effector functions such as antibody-dependent cellular cytotoxicity (ADCC) and cellular phagocytosis. In addition to the protein backbone, the homodimeric Fc domain contains two opposing N-linked glycans, which represent a further point of potential immunomodulation, independent of the Fc protein backbone. For example, a lack of core fucose usually attached to the IgG Fc glycan leads to enhanced ADCC activity, whereas a high level of terminal sialylation is associated with reduced inflammation. Significant growth in knowledge of Fc glycosylation over the last decade, combined with advancement in genetic engineering, has empowered glyco-engineering to fine-tune antibody therapeutics. This has culminated in the approval of two glyco-engineered antibodies for cancer therapy: the anti-CCR4 mogamulizumab approved in 2012 and the anti-CD20 obinutuzumab in 2013. We discuss here the technological platforms for antibody glyco-engineering and review the current clinical landscape of glyco-engineered antibodies.

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Section: Glyco-engineered Antibodies In Clinical Oncologymentioning

confidence: 99%

Section: Mogamulizumab the First Approved Glyco-engineered Mabmentioning

confidence: 99%

Improving Antibody-Based Cancer Therapeutics Through Glycan Engineering

Marshall

Cragg

et al. 2017

BioDrugs

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“…An anti-CXCL8 antibody is marketed in China for the treatment of psoriasis and antibodies targeting CCL2, CCL5, and CXCL10 are in clinical trials [236,237]. The antibody Mogamulizumab (KW-0761), directed against CCR4 [238], is marketed in Japan for adult T-cell leukemia-lymphoma. Recently, Griffiths et al have described the interesting example of "i-bodies," which are human single domain antibodies (human equivalents of shark V NAR ), that antagonize CXCR4 [239].…”

Section: Mdpimentioning

confidence: 99%

Regulation of Chemokine- Receptor Interactions and Functions

2018

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“…cutaneous T-cell lymphoma (CTCL) [4][5][6][7][8][9]. Mogamulizumab (also named as KW-0761, poteligeo) is a humanized, IgG1 kappa monoclonal antibody that is directed against CCR4 [9][10][11].…”

Section: Introductionmentioning

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) is the receptor for CCL22 and CCL17, which is 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 Treg cells, the mogamulizumab can boost antitumor immunity and achieve anti-tumor effects.Methods: We examined the PubMed and ClinicalTrials.gov without any language restrictions until 1 February 2020. Considering variability in different studies, the overall survival (OS), progression‐free survival (PFS), objective responses rate (ORR) and Hazard Ratio (HR) were selected to evaluate the efficacy. Besides, adverse events (AEs) were calculated to assess the safety.Results: When patients were treated with mogamulizumab monotherapy, the most common all-grade AEs were lymphopenia, infusion reaction, fever, rash and chills while lymphopenia, neutropenia and rash were the top 3 grade ≥3 AEs. In combination therapies, the top 3 all-grade AEs were neutropenia, anaemia, and lymphopenia, and lymphopenia is the most common grade ≥3 AE. Besides, the overall ORR is 0.430 (95% CI: 0.393-0.469) and the pooled mean PFS is 1.060 months (95% CI: 1.043-1.077) in mogamulizumab monotherapy. In combination therapies, the overall ORR is 0.203 (95% CI: 0.022-0.746) while the overall 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: On the basis of present evidence, we believed that mogamulizumab had clinically meaningful antitumor activity with acceptable toxicity which had a considerable potential in treating patients with cancers.

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Mogamulizumab for the treatment of cutaneous T-cell lymphoma: recent advances and clinical potential

Cited by 42 publications

References 19 publications

Improving Antibody-Based Cancer Therapeutics Through Glycan Engineering

Improving Antibody-Based Cancer Therapeutics Through Glycan Engineering

Regulation of Chemokine- Receptor Interactions and Functions

Safety and Efficacy Profile of Mogamulizumab (Poteligeo) in the Treatment of Cancers: An Update Evidence From 14 Studies

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