Mogamulizumab

Mogamulizumab (KW-0761) is a defucosylated humanized recombinant anti-CCR4 monoclonal antibody (MAb). Mogamulizumab can eliminate tumor cells by antibody-dependent cellular cytotoxicity (ADCC). Mogamulizumab can be used in the research of cancers, adult T-cell leukemia/lymphoma (ATLL), cutaneous T-cell lymphoma (CTCL)[1][2][3].

Signaling Pathways >> GPCR/G Protein >> CCR

Research Areas >> Cancer

Signaling Pathways >> Immunology/Inflammation >> CCR

Research Areas >> Inflammation/Immunology

CCR4

Mogamulizumab (10 μg/mL, 24 h) induces ADCC activity against CCR4-positive cell lines (SNT8, SNT16, SNK6, and KAI3) in the presence of PBMCs[2]. Mogamulizumab (10 μg/mL, 3 days) reduces the human T-lymphotropic virus type 1 (HTLV-1) proviral load and inhibits spontaneous proliferation in PBMCs from patients with HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP)[3]. Mogamulizumab (1 μg/mL, 5 days) eliminates the CD4+CCR4+ T cells in cultured PBMCs from patients with HAM/TSP[3].

Mogamulizumab (1 mg/kg, i.p., twice per week for 4 weeks) together with PBMC transplantation inhibits the growth of EBV-positive NK-cell lymphomas in a murine xenograft model[2]. Mogamulizumab (0.1 mg/kg, i.v., every other day) together with canine PBMCs (every fourth day)), inhibits tumor growth in canine bladder cancer-engrafted mouse model[4]. Mogamulizumab (0.01-1 mg/kg, i.v.) reduces circulating CD4+CCR4+ T cells, with no adverse effect in dogs[4]. Animal Model: Murine xenograft model, constructed by using the immunodeficient NOG mouse and the EBV-positive NK-cell lymphoma cell line (SNK6)[2] Dosage: 1 mg/kg Administration: Intraperitoneal injection (i.p.), together with PBMC transplantation; twice per week for 4 weeks. Result: Suppressed Tumor growth with vacuolar degeneration.

[1]. Duvic M, et al. Mogamulizumab for the treatment of cutaneous T-cell lymphoma: recent advances and clinical potential. Ther Adv Hematol. 2016 Jun;7(3):171-4.  

[2]. Kanazawa T, et al. Anti-CCR4 monoclonal antibody mogamulizumab for the treatment of EBV-associated T- and NK-cell lymphoproliferative diseases. Clin Cancer Res. 2014 Oct 1;20(19):5075-84.  

[3]. Yamauchi J, et al. Mogamulizumab, an anti-CCR4 antibody, targets human T-lymphotropic virus type 1-infected CD8+ and CD4+ T cells to treat associated myelopathy. J Infect Dis. 2015 Jan 15;211(2):238-48.  

[4]. Maeda S, et al. CCR4 Blockade Depletes Regulatory T Cells and Prolongs Survival in a Canine Model of Bladder Cancer. Cancer Immunol Res. 2019 Jul;7(7):1175-1187.