Monoclonal antibody 806 inhibits the growth of tumor xenografts expressingeither the de2-7 or amplified epidermal growth factor receptor (EGFR) but not wild-type EGFR

The monoclonal antibody (mAb) 806 was raised against the delta2-7 epidermal growth factor receptor (de2-7 EGFR or EGFRvIII), a truncated version of th e EGFR commonly expressed in glioma, Unexpectedly, mAb 806 also bound the E GFR expressed by cells exhibiting amplification of the EGFR gene but not to cells or normal tissue expressing the wild-type receptor in the absence of gene amplification. The unique specificity of mAb 806 offers an advantage over current EGFR antibodies, which all display significant binding to the liver and skin in humans, Therefore, we examined the antitumor activity of mAb 806 against human tumor xenografts grown in nude mice. The growth of U8 7 MG xenografts, a glioma cell line that endogenously expresses similar to 10(5) EGFRs in the absence of gene amplification, was not inhibited by mAb 806, In contrast, mAb 806 significantly inhibited the growth of U87 MG xeno grafts transfected with the de2-7 EGFR in a dose-dependent manner using bot h preventative and established tumor models. Significantly, U87 MG cells tr ansfected with the wild-type EGFR, which increased expression to similar to 10(6) EGFRs/cell and mimics the situation of gene amplification, were also inhibited by mAb 806 when grown as xenografts in nude mice. Xenografts tre ated with mAb 806 all displayed large areas of necrosis that were absent in control tumors. This reduced xenograft viability was not mediated by recep tor down-regulation or clonal selection because levels of antigen expressio n were similar in control and treated groups. The antitumor effect of mAb 8 06 was not restricted to U87 MG cells because the antibody inhibited the gr owth of new and established A431 xenografts, a cell line expressing > 10(6) EGFRs/cell. This study demonstrates that mAb 806 possesses significant ant itumor activity.