Recombinant Human Antibody (MR1) is capable of binding to EGFRvIII dodecapeptide (EEKKGNYVVTDH), expressed in HEK 293 cells. Expressed as the combination of a heavy chain (HC) containing VH from anti-EGFRvIII dodecapeptide (EEKKGNYVVTDH) mAb and CH1-3 region of human IgG1 and a light chain (LC) encoding VL from anti-EGFRvIII dodecapeptide (EEKKGNYVVTDH) mAb and CL of human kappa light chain. Exists as a disulfide linked dimer of the HC and LC hetero-dimer under non-reducing condition. Necitumumab is a recombinant human IgG1 monoclonal antibody that binds to the human epidermal growth factor receptor (EGFR) and blocks the binding of EGFR to its ligands. IMC-11F8 is a fully human antibody that has similar antitumor potency as the chimeric cetuximab/Erbitux and might represent a safer therapeutic alternative.
Figure 1 Epidermal growth factor receptor variant III (EGFRvIII) recognition by different antibodies.
(A) Lysates of EGFRvIII-transfected and parental A431 and HEK293T cells were analyzed by immunoblot using the stated antibodies for detection and b-actin as a loading control. Arrows indicate the expected molecular weights of wild-type (wt) EGFR and EGFRvIII, which appears as a double band. 13.1.2 exclusively detected EGFRvIII, whereas ch806 and MR1-1 also bound to wt EGFR on nontransfected cells. (B) Indirect immunofluorescence revealed a similar binding of EGFRvIII antibodies to EGFRvIII-expressing A431 (A431-vIII) and HEK293T (HEK293T-vIII) cells (lower panel). Additional binding to A431 cells was obtained with MR1-1 (grey line) and ch806 (black line). MR1-1 also displayed reactivity with HEK293T cells, whereas 13.1.2 (dotted line) only bound to EGFRvIIItransfected cells. Zalutumumab (black fill) recognized wt EGFR and EGFRvIII. An irrelevant IgG1 antibody (KLH) served as a control (grey fill).
Klausz, K. , Berger, S. , Bueren, J. J. L. V. , Derer, S. , Lohse, S. , & Dechant, M. , et al. (2011). Complement-mediated tumor-specific cell lysis by antibody combinations targeting epidermal growth factor receptor (egfr) and its variant iii (egfrviii). Cancer Science, 102(10), 1761-1768.
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