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EGF can stimulate cell proliferation in normal tissue and in malignant lesions by activating EGF receptor (EGFR) tyrosine kinase signaling pathways. EGFR is frequently overexpressed in many cancers including breast, colon, head and neck, glioblastoma, gastric, and squamous cell carcinoma and is associated with more aggressive cancer subtypes. Antibodies are attractive candidates for cancer therapeutics not only because of their exquisite specificity to the target and ability to inhibit cell signaling, but also because of their long half-life in serum and the ability to induce tumor antigen-specific immune responses.EGFR single chain antibodies, which can generate Fab and IgG from single chain antibodies, have important implications for intrinsic affinity and valence-mediated affinity for tumor cell binding, EGFR phosphorylation, and inhibition of tumor cell proliferation.