Anti-EGFR [2F8 (Zalutumumab; HuMax-EGFR)]

Absolute Antibody

Anti-EGFR [2F8 (Zalutumumab; HuMax-EGFR)]

9

This antibody binds domain III of the human epidermal growth factor receptor (EGFR).

This antibody blocks the binding of EGF and TGF-alpha to the EGFR. At saturating concentrations, 2F8 completely blocked EGF-R signaling and inhibited the in vitro proliferation of EGF-R-overexpressing A431 cells. At much lower concentrations, associated with low receptor occupancy, 2F8 induced efficient Ab-dependent cell-mediated cytotoxicity (ADCC) in vitro. In vivo studies showed potent antitumor effects in models with A431 tumor xenografts in athymic mice. Flow cytometry was used to analyze the binding of mAb 2F8 to EGFR overexpressing A431 cells. mAb 2F8 was found to bind to membrane-associated EGF-R with an EC50 of approximately 1 microg/ml (7 nM). The ability of mAb 2F8 to block ligand-induced receptor phosphorylation was determined using immunoblotting. ELISA was used to determine whether mAb 2F8 had a functional C1q binding cite (Bleeker et al., 2004). Phase I/II clinical trials and pharmacokinetic studies in patients with advanced squamous cell carcinoma of the head and neck revealsed that 2F8/HuMax-EGFR can be safely administered in doses upto 8 mg/kg (Bastholt et al., 2007) Antibody 2F8 binds the domain III of the EGFR and locks it into a very compact and inactice conformation. Biochemical analyses showed bivalent binding of 2F8 to provide potent inhibition of EGFR signaling (Beuren et al., 2008). EGFRvIII-specific CDC was significantly enhanced when zalutumumab was combined with a Fc-engineered variant of antibody MR1-1 (Klausz et al., 2011).

Flow Cytometry, Western Blot, ELISA

Research Use Only

Monoclonal

2F8 (Zalutumumab; HuMax-EGFR)

EGFR

epidermal growth factor receptor

avian erythroblastic leukemia viral (v-erb-b) oncogene homolog; cell growth inhibiting protein 40; cell proliferation-inducing protein 61; epidermal growth factor receptor; epidermal growth factor receptor tyrosine kinase domain; ERBB; ERBB1; erb-b2 receptor tyrosine kinase 1; ERRP; HER1; mENA; NISBD2; PIG61; proto-oncogene c-ErbB-1; receptor tyrosine-protein kinase erbB-1

Mouse

IgG2b

Epidermal growth factor receptor

This chimeric mouse antibody was made using the variable domain sequences of the original Human IgG1 format, for improved compatibility with existing reagents, assays and techniques.

Human

-20°C,2°C to 8°C

12352203