title: Distribution of humanized MAb 425 (EMD 62,000) in rats and specific localization in tumor-bearing nude mice.
abstract: The murine MAb 425 (IgG2a) directed against human epidermal growth factor receptor is considered to have therapeutic potential in glioma patients. In order to circumvent immune response in clinical use, the MAb 425 was humanized by CDR-grafting (IgG1). We have studied the distribution of reshaped MAb 425 (EMD 62,000) in Wistar rats and the specific localization in female nude mice bearing human mamma carcinoma xenografts. The 125I-labelled MAb 425 was administered intravenously in a single dose (1 mg/kg) using unspecific human IgG1 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, radioactivity was bound exclusively to the tumour. Similar results were obtained with the murine monoclonal antibody. Quantitative studies exhibited a tumour-blood ratio of about 5. The study demonstrates that the humanized MAb 425 is selectively localized in human mamma carcinoma xenografted to athymic mice.
authors.affiliation: E. MERCK, Institute of Pharmacokinetics and Metabolism, Grafing, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Steiner
authors.forename: J
authors.initials: J
authors.lastname: Haunschild
authors.forename: H P
authors.initials: HP
authors.lastname: Faro
authors.forename: R
authors.initials: R
authors.lastname: Senekowitsch
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics*; D001345:Autoradiography; D001943:Breast Neoplasms; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism*; D066246:ErbB Receptors / Q000032:analysis* / Q000276:immunology; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000032:analysis; D009368:Neoplasm Transplantation; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D066246:ErbB Receptors