title: The effect of circulating antigen on the biodistribution of the engineered human antibody hCTM01 in a nude mice model.
abstract: Clinical studies are currently underway to assess the biodistribution and therapeutic potential of the genetically engineered human antibody hCTM01 directed against polymorphic epithelial mucin (PEM) in patients with ovarian carcinoma. The present study was undertaken to assess the effect of circulating PEM antigen on the biodistribution of the anti-PEM antibody in mice bearing MUC-1 transfected adenocarcinoma cell lines. Tumour xenografts were established from three cell lines: 413-BCR, which expressed antigen on the cell surface and also shed antigen into the circulation, E3P23, which expressed the antigen but did not shed into the circulation, and a negative control (410.4 MUCI). Groups of five mice were injected with 1.0 mg/kg antibody, imaged after 72 h and then sacrificed, followed by assay of tissue uptake. The results showed a clear difference in the tumour and liver uptake, with the non-secreting cell line showing almost twice the tumour uptake and approximately 20% of the liver uptake of the secreting cell line.
authors.affiliation: Department of Obstetrics and Gynaecology, University Hospital, Queen's Medical Centre, Nottingham, UK.
authors.forename: Q
authors.initials: Q
authors.lastname: Davies
authors.forename: A C
authors.initials: AC
authors.lastname: Perkins
authors.forename: M
authors.initials: M
authors.lastname: Frier
authors.forename: S
authors.initials: S
authors.lastname: Watson
authors.forename: E
authors.initials: E
authors.lastname: Lalani
authors.forename: E M
authors.initials: EM
authors.lastname: Symonds
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging* / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007205:Indium Radioisotopes; D008099:Liver / Q000000981:diagnostic imaging*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D018396:Mucin-1 / Q000276:immunology*; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy; D016719:Radioimmunodetection; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
chemical_list: D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; D018396:Mucin-1