Anti-hEGFR-hIgG1fut

Anti-hEGFR-hIgG1fut features the 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 is a non-fucosylated antibody. The absence of the fucose residue from the N-glycans of IgG-Fc results in dramatic enhancement of antibody-dependent cellular cytotoxicity (ADCC) without any detectable change in complement-dependent cytotoxicity (CDC) or antigen binding capability [4,5].

This antibody was generated by recombinant DNA technology. It has been produced in CHO cells that are deficient for fucosylation and purified by affinity chromatography with protein G.

Applications:

Anti-hEGFR-hIgG1fut can be used with Anti-hEGFR-hIgG1 to compare the ADCC activity.

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. Yamane-Ohnuki N. & Satoh M., 2009. Production of therapeutic antibodies with controlled fucosylation. corresponding MAbs. 1:230–236.
5. Mizushima T., 2011. Structural basis for improved efficacy of therapeutic antibodies on defucosylation of their Fc glycans. Genes Cells. 16: 1071–80.