Multicenter Phase II Study of Mogamulizumab (KW-0761), a Defucosylated Anti-CC Chemokine Receptor 4 Antibody, in Patients With Relapsed Peripheral T-Cell Lymphoma and Cutaneous T-Cell Lymphoma

Ogura, Michinori; Ishida, Takashi; Hatake, Kiyohiko; Taniwaki, Masafumi; Ando, Kiyoshi; Tobinai, Kensei; Fujimoto, Katsuya; Yamamoto, Kazuhito; Miyamoto, Toshihiro; Uike, Naokuni; Tanimoto, Mitsune; Tsukasaki, Kunihiro; Ishizawa, Kenichi; Suzumiya, Junji; Inagaki, Hiroshi; Tamura, Kazuo; Akinaga, Shiro; Tomonaga, Masao; Ueda, Ryuzo

doi:10.1200/jco.2013.52.0924

Cited by 323 publications

(231 citation statements)

References 39 publications

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“…C-C chemokine receptor 4 (CCR4) is expressed on NKTL and might be a suitable target for the antibody therapy. Because CCR4 is a receptor of CCL22 that activates Treg as discussed above, CCR4-targeted therapy would damage both CCR4-positive NKTL cells and Treg with manageable adverse events [70]. Indeed, we have shown that mogamulizumab, a defucosylated anti-CCR4 antibody, enhances the killing of NKTL cells by normal NK cells via antibody-dependent cell-mediated cytotoxicity [17].…”

Section: Antibody Therapiesmentioning

confidence: 78%

Novel Targets for Natural Killer/T-cell Lymphoma Immunotherapy

2015

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SummaryExtranodal natural killer/T-cell lymphoma, nasal type (NKTL) is a rare but highly aggressive Epstein-Barr virus-related malignancy, which mainly occurs in nasopharygeal and nasal/paranasal areas. In addition to its high prevalence in Asian, Central American and South American populations, its incidence rate has been gradually increasing in Western countries. The current mainstay of treatment is a combination of multiple chemotherapies and irradiation. Although chemoradiotherapy can cure NKTL, it often causes severe and fatal adverse events. Because a growing body of evidence suggests that immunotherapy is effective against hematological malignancies, this treatment could provide an alternative to chemoradiotherapy for treatment of NKTL. In this review, we focus on how recent findings could be used to develop efficient immunotherapies against NKTL.

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Section: Antibody Therapiesmentioning

confidence: 78%

Novel Targets for Natural Killer/T-cell Lymphoma Immunotherapy

2015

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“…A phase 2 study of mogamulizumab (1.0 mg/kg) in Japanese patients with CCR4-positive PTCL and CTCL has been recently reported. 32 This study enrolled a small number of CTCL patients (n 5 8) with only relapsed disease. However, the ORR of 35% was similar to the rate of 36.8% among the 38 patients in our study.…”

Section: Discussionmentioning

confidence: 99%

Phase 1/2 study of mogamulizumab, a defucosylated anti-CCR4 antibody, in previously treated patients with cutaneous T-cell lymphoma

Duvic

Pinter‐Brown

Foss

et al. 2015

Blood

210

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“…Mogamulizumab is a defucosylated and humanized monoclonal antibody to CCR4 that shows marked effects against ATL (12) and peripheral T-cell lymphoma (13). It works directly by depleting tumor cells and indirectly by increasing antitumor immunity through eTreg depletion via antibody-dependent cellular cytotoxicity (3).…”

Section: Introductionmentioning

confidence: 99%

Effector Regulatory T Cells Reflect the Equilibrium between Antitumor Immunity and Autoimmunity in Adult T-cell Leukemia

Ureshino

Shindo

Nishikawa

et al. 2016

Cancer Immunology Research

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The regulatory T cells (Treg) with the most potent immunosuppressive activity are the effector Tregs (eTreg) with a CD45RA -Foxp3 þþ CCR4 þ phenotype. Adult T-cell leukemia (ATL) cells often share the Treg phenotype and also express CCR4. Although mogamulizumab, a monoclonal antibody to CCR4, shows marked antitumor effects against ATL and peripheral T-cell lymphoma, concerns have been raised that it may induce severe autoimmune immunopathology by depleting eTregs. Here, we present case reports for two patients with ATL who responded to mogamulizumab but developed a severe skin rash and autoimmune brainstem encephalitis. Deep sequencing of the T-cell receptor revealed that ATL cells and naturally occurring Tregs within the cell population with a Treg phenotype can be clearly distinguished according to CADM1 expression. The onset of skin rash and brainstem encephalitis was coincident with eTreg depletion from the peripheral blood, whereas ATL relapses were coincident with eTreg recovery. These results imply that eTreg numbers in the peripheral blood sensitively reflect the equilibrium between antitumor immunity and autoimmunity, and that mogamulizumab might suppress ATL until the eTreg population recovers. Close monitoring of eTreg numbers is crucial if we are to provide immunomodulatory treatments that target malignancy without severe adverse events.

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Multicenter Phase II Study of Mogamulizumab (KW-0761), a Defucosylated Anti-CC Chemokine Receptor 4 Antibody, in Patients With Relapsed Peripheral T-Cell Lymphoma and Cutaneous T-Cell Lymphoma

Abstract: Mogamulizumab exhibited clinically meaningful antitumor activity in patients with relapsed PTCL and CTCL, with an acceptable toxicity profile. Further investigation of mogamulizumab for treatment of T-cell lymphoma is warranted.

Cited by 323 publications

References 39 publications

Novel Targets for Natural Killer/T-cell Lymphoma Immunotherapy

Novel Targets for Natural Killer/T-cell Lymphoma Immunotherapy

Phase 1/2 study of mogamulizumab, a defucosylated anti-CCR4 antibody, in previously treated patients with cutaneous T-cell lymphoma

Effector Regulatory T Cells Reflect the Equilibrium between Antitumor Immunity and Autoimmunity in Adult T-cell Leukemia

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