Supplementary Methods, Figures S1-S11, and Table Legends from Enhanced Targeting of the EGFR Network with MM-151, an Oligoclonal Anti-EGFR Antibody Therapeutic

Abstract

<p>Supplementary Methods, Figures S1-S11, and Table Legends. Supplementary Methods: description of methods used in the Supplementary figures, expanded description of ELISA assays, and description of the computational model of multiple EGFR ligand antagonists. Supplementary Figure S1: Monoclonal EGFR antibodies poorly block signal amplification by high-affinity EGFR ligands. Supplementary Figure S2: Hierarchical clustering of EGFR ligand expression in primary colon, head and neck, and lung tumors. Supplementary Figure S3: Trends observed in EGFR ligand expression in TCGA data set are similarly apparent in primary colorectal samples analyzed by RT-qPCR. Supplementary Figure S4: Relative expression of EGFR ligands varies across cancer indications. Supplementary Figure S5: Simulated activity of a combination of two ligand antagonists versus single antagonists as a function of ligand affinity. Supplementary Figure S6: MM-151 antibodies have non-overlapping epitopes and can simultaneously engage the same EGF receptor molecule. Supplementary Figure S7: MM-151 elicits superior ligand antagonism. Supplementary Figure S8: MM-151 promotes potent down-regulation of EGFR that is dependent upon the oligoclonal combination of bivalent antibodies. Supplementary Figure S9: MM-151 promotes both antibody-dependent cell-mediated (ADCC) and complement-dependent (CDC) cytotoxicity. Supplementary Figure S10: Cell proliferation stimulated by high-affinity ligands is partially or completely resistant to cetuximab treatment but still sensitive to MM-151 treatment. Supplementary Figure S11: MM-151 overcomes signal amplification driven by high-affinity ligand. Legends for Supplementary Tables S1-S8.</p>