title: Clinical Application of Anti-CCR4 Monoclonal Antibody.
abstract: 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 Fcx03B3; 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-FOXP3highCD4+ 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.
authors.affiliation: Department of Tumor Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Ueda
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D015972:Gene Expression Regulation, Neoplastic; D019337:Hematologic Neoplasms / Q000188:drug therapy; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D016411:Lymphoma, T-Cell, Peripheral / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D054398:Receptors, CCR4 / Q000037:antagonists & inhibitors*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology*; D019139:Tumor Escape; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C515354:CCR4 protein, human; D054398:Receptors, CCR4; C549035:mogamulizumab