Journal Article

Clinical Application of Anti-CCR4 Monoclonal Antibody

Ueda, Ryuzo

2015

Overview

Mogamulizumab (KW-0761) is a humanized anti-CCR4 monoclonal antibody with a defucosylated Fc region (Potelligent® Technology), which markedly enhances antibody-dependent cellular cytotoxicity by increasing its binding affinity to the Fcγ receptor expressed on effector cells. It is an effective agent for patients with CCR4-positive adult T-cell leukemia and peripheral T-cell lymphoma, for which no standard therapy exists, and it has an acceptable toxicity profile. In addition, because CCR4 is expressed on CD45RA - FOXP3 high CD4 + effector regulatory T (Treg) cells, it is an even more attractive target, because Treg cells involved in the tumor escape from host immunity in the tumor microenvironment. Based on this concept, we conducted a clinical study of mogamulizumab for the treatment of CCR4-negative advanced or recurrent solid cancer, with the aim of depleting effector Treg cells and thus boosting anti-cancer immune responses. In this study, mogamulizumab infusion at doses ranging from 0.1 to 1.0 mg/kg was safe and well tolerated. Four of 10 patients showed stable disease during treatment and showed long-term survival. Mogamulizumab efficiently depleted effector Treg cells even at the lowest dose of 0.1 mg/kg, and an augmentation or induction of specific immune responses to cancer/testis antigens was observed in some patients. In the near future, a novel immunotherapy targeting Treg cells with mogamulizumab will be offered to patients with different types of cancer.

• Publisher: S. Karger AG
• Subject: Antibodies, Monoclonal, Humanized - pharmacology / Antibodies, Monoclonal, Humanized - therapeutic use / Antineoplastic Agents - pharmacology / Antineoplastic Agents - therapeutic use / Cancer / Care and treatment / Clinical Trials, Phase I as Topic / Gene Expression Regulation, Neoplastic / Health aspects / Hematologic Neoplasms - drug therapy / Humans / Immunotherapy / Kimura Memorial Lecture / Leukemia-Lymphoma, Adult T-Cell - drug therapy / Leukemia-Lymphoma, Adult T-Cell - immunology / Leukemia-Lymphoma, Adult T-Cell - metabolism / Lymphocytes / Lymphoma, T-Cell, Peripheral - drug therapy / Lymphoma, T-Cell, Peripheral - immunology / Lymphoma, T-Cell, Peripheral - metabolism / Methods / Monoclonal antibodies / Oncology, Experimental / Patient outcomes / Receptors, CCR4 - antagonists & inhibitors / T-Lymphocytes, Regulatory - drug effects / T-Lymphocytes, Regulatory - immunology / Tumor Escape / Tumor Microenvironment - immunology
• ISBN: 9783318055030, 3318055034