Anti-hEGFR-hIgG1NQ

Anti-hEGFR-hIgG1NQ features a mutated constant region of the human IgG1 isotype and the variable region of cetuximab. Cetuximab is a chimeric human/mouse IgG1 monoclonal antibody that targets EGFR, a cell surface receptor overexpressed in many types of cancer. EGFR is activated by binding specific ligands, including epidermal growth factor and transforming growth factor-α. Activation of EGFR promotes cell proliferation and survival, as well as angiogenesis, leading to tumor growth and metastasis. Binding of cetuximab to EGFR blocks ligand-receptor binding and induces receptor internalization and subsequent degradation. Consequently, it blocks downstream pathways which regulate cell growth and angiogenesis. In addition, it induces cell death through antibody-dependent cell-mediated cytotoxicity (ADCC) [1,2]. Cetuximab has been approved by the FDA for the treatment of metastatic colorectal cancer and metastatic squamous cell carcinoma of the head and neck  [3].

Anti-hEGFR-hIgG1 contains a N-glycosylation mutation of the constant region of the human IgG1 where potential asparagine (N) glycosylation sites are substituted by glutamine (Q) residues resulting in the production of a non-glycosylated antibody. Glycosylation of an antibody has no effect on antigen binding but is essential for Fc receptor-mediated activity [4]. In non-glycosylated antibodies the effector mechanisms mediated through the Fc receptors types (FcγRI, FcγRII, FcγRIII) and the C1q component of complement are severely compromised or ablated [5]. This antibody has been produced in CHO cells and purified by affinity chromatography with protein G.

Applications:  

Anti-hEGFR-hIgG1NQ can be used with Anti-hEGFR-hIgG1 to study the impact of effector functions.

References:

1. Kurai J. et al., 2007. Antibody-dependent cellular cytotoxicity mediated by cetuximab against lung cancer cell lines. Clin Cancer Res. 3(5):1552-61.
2. Kimura H. et al., 2007. Antibody-dependent cellular cytotoxicity of cetuximab against tumor cells with wild-type or mutant epidermal growth factor receptor. Cancer Sci. 98(8):1275-80.
3. Vincenzi B. et al., 2010. Cetuximab: from bench to bedside. Curr Cancer Drug Targets. 10(1):80-95.
4. Arnold J. et al., 2007. The impact of glycosylation on the biological function and structure of human immunoglobulins. Annu Rev Immunol 25:21-50.
5. Jefferis R., 2009. Glycosylation as a strategy to improve antibody-based therapeutics. Nat Rev Drug Discov. 8:226-34.