Mogamulizumab (KW-0761) is a humanized deglycosylated IgG1 mAb that targets CC chemokine receptor 4 (CCR4). This antibody can enhance ADCC effect by removing fucose content on the Fc region of mogamulizumab IgG. Through this, the binding affinity of the FcγR on the surface of non-specific effector cells (such as killer (NK) cells and macrophages/monocytes) to the Fc region of the IgG molecule is enhanced, thereby eliminating tumor cells. This MOA not only increases activity of cytotoxic cells, but also promotes the release of cytoplasmic lyase, granzymes, perforin-containing particles and tumor necrosis factor (TNF) that induces antibody-targeted cell lysis.
Mogamulizumab is a novel type II glycosylation-engineered humanized anti-CCR4 monoclonal antibody developed to meet the needs for an agent with stronger effects on CCR4-positive cancers. The glycosylation process used to develop this agent is achieved by reducing the fucosylation in the Fc region of the mAb molecule, resulting in an increased binding affinity of the agent for the FcγRIIIa receptor on immune effector cells.
Fig.2 Glycoengineering by defucosylation of immunoglobulin G oligosaccharides in the Fc region of Mogamulizumab.
Mogamulizumab is a cell clone of a deglycosylated mAb produced using ADCC-enhanced technology, meaning that its complex type has no fucose in the constant (Fc) region on the carbohydrate structure of cells. Mogamulizumab has ADCC activity but does not exhibit any CDC activity or neutralizing ability to CCR4 ligand. Mogamulizumab has a complementarity determining region (CDR) CC-chemokine receptor 4 (CCR4) derived from mouse anti-human, which binds to CCR4 antigen on the surface of T cells and induces ADCC. The MoA of Mogamulizumab is established by three elements: CCR4 antigen on target cells, Mogamulizumab antibody, and gamma receptor IIIa (FcγRIIIa) interacting with Fc on natural killer (NK) effector cells. The MoA is depicted below.
Fig.3 Mechanisms of action of Mogamulizumab.
Glycan profiles of Mogamulizumab by hydrophilic interaction liquid chromatography (HILIC).
KW-0761 mediates effective in vitro ADCC activity against primary Adult T-Cell Leukemia Lymphoma (ATLL) cells in the autologous environment.
Mogamulizumab has obtained FDA approval for Cutaneous T-cell lymphoma (CTCL) and Adult T-Cell Leukemia Lymphoma (ATLL) based on the results confirmed by the third phase MAVORIC study.
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Creative Biolabs provides luciferase-based ADCC assay. This Jurkat cell based assay is pioneered by Creative Biolabs, and the methodology is very well accepted by the field. See attached ADCC Reporter Assay Protocol for further details.
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