An array of
cell-surface antigens expressed by human
cancers have been identified as targets for antibody-based
therapies. The great majority of these
antibodies do not have specificity for
cancer but recognize
antigens expressed on a range of normal cell types (
differentiation antigens). Over the past two decades, our group has analyzed thousands of mouse
monoclonal antibodies for
cancer specificity and identified a battery of
antibodies with limited representation on normal human cells. The most
tumor-specific of these
antibodies is 806, an antibody that detects a unique
epitope on the
epidermal growth factor receptor (EGFR) that is exposed only on overexpressed, mutant, or
ligand-activated forms of the receptor in
cancer. In vitro immunohistochemical specificity analysis shows little or no detectable 806 reactivity with normal tissues, even those with high levels of wild-type (wt)EGFR expression. Preclinical studies have demonstrated that 806 specifically targets a subset of EGFR expressed on
tumor cells, and has significant anti-
tumor effects on human
tumor xenografts, primarily through abrogation of signaling pathways. The present clinical study was designed to examine the in vivo specificity of a chimeric form of
mAb 806 (ch806) in a
tumor targeting/biodistribution/pharmacokinetic analysis in patients with diverse
tumor types. ch806 showed excellent targeting of
tumor sites in all patients, no evidence of normal tissue uptake, and no significant toxicity. These in vitro and in vivo characteristics of ch806 distinguish it from all other
antibodies targeting EGFR.