Target mediated disposition of T84.66, a monoclonal anti-CEA antibody: Application in the detection of colorectal cancer xenografts

• Published in: mAbs Vol. 2; no. 1; pp. 67 - 72
• Main Authors: Urva, Shweta R., Balthasar, Joseph P.
• Format: Journal Article
• Language: English
• Published: United States Landes Bioscience 01.01.2010
• Subjects: Adenocarcinoma - diagnosis; Adenocarcinoma - immunology; Adenocarcinoma - metabolism; Animals; Antibodies, Monoclonal - pharmacokinetics; Binding; Biology; Bioscience; Brief Report; Calcium; Cancer; Carcinoembryonic Antigen - immunology; Carcinoembryonic Antigen - metabolism; Cell; Cell Line, Tumor; Colorectal Neoplasms - diagnosis; Colorectal Neoplasms - immunology; Colorectal Neoplasms - metabolism; Cycle; Disease Models, Animal; Humans; Landes; Metabolic Clearance Rate; Mice; Mice, Nude; Organogenesis; Prognosis; Proteins; Sensitivity and Specificity; Transplantation, Heterologous - methods; Tumor Burden - immunology
• ISSN: 1942-0862; 1942-0870; 1942-0870
• DOI: 10.4161/mabs.2.1.10781

Carcinoembryonic antigen (CEA) is a glycosylated cell surface antigen known to be highly over-expressed in several adenocarcinomas, including colorectal cancer, while demonstrating limited expression in normal tissues. Prior work has shown that the plasma clearance of T84.66, a monoclonal anti-CEA antibody, is enhanced by several-fold in a CEA-expressing xenograft mouse model, suggesting the presence of a target mediated elimination pathway. The purpose of this study is to investigate the influence of tumor volume on the plasma clearance of T84.66, and test the hypothesis that the plasma pharmacokinetics of T84.66 may be used as a sensitive and selective test for the diagnosis of CEA-positive tumors. T84.66 plasma pharmacokinetics were studied following intravenous (i.v.) administration of a 1 mg/kg dose in animals without tumor and mice bearing low (20–75 mm3), medium (400–570 mm3), and high volume (800–1200 mm3) LS174T xenografts.