Margetuximab

Specification

• Cat#: THA-0123
• Product Name: Margetuximab
• Description: Margetuximab is an Fc-engineered human/mouse chimeric IgG1魏 anti-HER2 monoclonal antibody indicated for patients with HER2-positive metastatic breast cancer.
• Introduction: The HER2 oncoprotein, the product of the human ERBB2/mouse neu genes, is a member of the HER family of receptor tyrosine kinases that includes the epidermal growth factor receptor (EGFR). Of the various subtypes of breast cancer, HER2-positive breast cancer is characterized by ERBB2 overexpression, a higher grade, a more aggressive phenotype, and a worse prognosis compared to HER2-negative cancer. The introduction of trastuzumab improved patient outcomes in HER2-positive breast cancer, but notably depended substantially on polymorphisms in the FcγRIIIA/CD16A receptor, whereby low affinity 158F CD16A variants are associated with shorter progression-free survival and worse patient outcomes. Margetuximab (formerly MGAH22) is an Fc-engineered human/mouse chimeric anti-HER2 IgG1κ monoclonal antibody derived from the same mouse 4D5 clone that trastuzumab is derived from and is produced in Chinese Hamster Ovary (CHO) culture. Margetuximab binds to the same epitope on the HER2 extracellular domain and induces the same effects as trastuzumab. However, due to its modified Fc region, margetuximab binds with higher affinity to both CD16A variants and exhibits weaker binding to the inhibitory CD32B Fc receptor, resulting in more efficient antibody-dependent cell-mediated cytotoxicity (ADCC) and increased efficacy compared to trastuzumab. Margextuximab was granted FDA approval on December 16, 2020, and is currently marketed under the trademark MARGENZA鈩?by MacroGenics, Inc.
• Purity: >99% by SDS-Page and HPLC analysis
• Appearance: Liquid

Pharmaceutical Information

• Pharmacodynamics: Margetuximab is a chimeric IgG1κ monoclonal antibody (mAb) directed against the extracellular domain of the human epidermal growth factor receptor 2 (HER2) cell-surface protein. Also, margetuximab has an engineered Fc region that alters its affinity for the CD16A and CD32B effector cell receptors resulting in increased antibody-dependent cell-mediated cytotoxicity (ADCC). To date, the exposure-response and time course pharmacodynamic relationships of margetuximab remain incompletely characterized. Although generally well-tolerated, margetuximab carries a risk of infusion-related reactions, including symptoms such as fever, fatigue, nausea, vomiting, headache, tachycardia, hypotension, and cutaneous manifestations such as a rash or urticaria; infusion reactions may require alterations to the infusion or, in serious reactions, discontinuation.