DISTRIBUTION OF HUMANIZED MAB-425 (EMD-62000) IN RATS AND SPECIFIC LOCALIZATION IN TUMOR-BEARING NUDE-MICE

The murine MAb 425 (IgG2a) directed against human epidermal growth fac tor receptor is considered to have therapeutic potential in glioma pat ients. In order to circumvent immune response in clinical use, the MAb 425 was humanized by CDR-grafting (IgGl). We have studied the distrib ution of reshaped MAb 425 (EMD 62 000) in Wistar rats and the specific localization in female nude mice bearing human mamma carcinoma xenogr afts. The I-125-labelled MAb 425 was administered intravenously in a s ingle dose (1 mg/kg) using unspecific human IgGl antibody as control. The biodistribution was investigated both quantitatively and by whole- body autoradiography. The autoradiographs showed a selective uptake of radioactivity by the tumour tissue. 15 days after administration, rad ioactivity was bound exclusively to the tumour. Similar results were o btained with the murine monoclonal antibody. Quantitative studies exhi bited a tumour-blood ratio of about 5. The study demonstrates that the humanized MAb 425 is selectively localized in human mamma carcinoma x enografted to athymic mice.