Targeting Cancer Micrometastases with Monoclonal Antibodies: A Binding-Site Barrier

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 92; no. 19; pp. 8999 - 9003
• Main Authors: Saga, Tsuneo, Neumann, Ronald D., Heya, Toshiro, Sato, Jun, Kinuya, Seigo, Le, Nhat, Paik, Chang H., Weinstein, John N
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 12.09.1995; National Acad Sciences; National Academy of Sciences
• Subjects: Animals; Antibodies; Antibodies, Monoclonal - pharmacokinetics; Antibodies, Monoclonal - therapeutic use; Antibodies, Neoplasm - therapeutic use; Antibody Specificity; Autoradiography; Bile Duct Neoplasms - pathology; Blood vessels; Cancer; Carcinoma - therapy; Dosage; Guinea Pigs; Immunohistochemistry; Immunotherapy - methods; Lung - pathology; Lung Neoplasms - secondary; Lung Neoplasms - therapy; Lungs; Medical research; Monoclonal antibodies; Nodules; Radioactive decay; Radiotherapy; Tumors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.92.19.8999

Monoclonal antibodies penetrate bulky tumors poorly after intravenous administration, in part because of specific binding to the target antigen. Experiments presented here demonstrate an analogous phenomenon in micrometastases; poor antibody penetration, attributable to a "binding-site barrier" phenomenon, can be seen in guinea pig micrometastases as small as 300 μm in diameter. Increasing the dose of antibody can partially overcome this limitation, but at a cost in specificity.