Anti-hEGFR-hIgG4 (S228P)

Anti-hEGFR-hIgG4 (S228P) features the constant region of the human IgG4 (S228P) isotype and the variable region of cetuximab. Cetuximab is a chimeric human/mouse IgG1 monoclonal antibody that targets epidermal growth factor receptor (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, cetuximab blocks downstream pathways which regulate cell growth and angiogenesis.

In addition, cetuximab 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-hIgG4 (S228P) contains an engineered hinge region mutation (S228P) designed to prevent exchange of IgG4 molecules.

Anti-hEGFR-hIgG4 (S228P) was generated by recombinant DNA technology. It has been produced in CHO cells and purified by affinity chromatography with protein G.

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. Antibodydependent 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.