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JNCI Journal of the National Cancer Institute 1991 83(3):200-205; doi:10.1093/jnci/83.3.200
© 1991 by Oxford University Press
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Journal of the National Cancer Institute, Vol. 83, No. 3, 200-205, February 6, 1991
© 1991 Oxford University Press

Diffusion and Binding of Monoclonal Antibody TNT-1 in Multicellular Tumor Spheroids

Feng-Ming Chen*, Eric B. Hansen, Clive R. Taylor, Alan L. Epstein

Department of Pathology, University of Southern California School of Medicine Los Angeles, Calif.

*Correspondence to: Feng-Ming Chen, PhD, Department of Diagnostic Radiology, City of Hope National Medical Center, 1500 E Duarte Rd, Duarte, CA 91010–0269.

Tumor spheroids of HT-29 human colon adenocarcinoma and A375 melanoma were established to investigate the uptake and clearance kinetics of TNT-1, a monoclonal antibody that targets ne-crotic cells of tumors. Our data reveal that there was rapid uptake of TNT-1 and its F(ab‘)2 fragment in both spheroid models, whereas an antibody of irrelevant specificity, Lym-1, and its F(ab’)2 fragment bound poorly to the spheroids. Unlike previously reported monoclonal antibodies to tumor cell-surface antigens, TNT-1 showed 1) a linear uptake that increased over time without saturation in tumor spheroids and 2) an unexpected uptake by a sub-population of cells in the viable outer rim of the spheroids. These preclinical studies provide important information concerning the therapeutic potential of TNT monoclonal antibodies for the treatment of cancer and micro-metastases. [J Natl Cancer Inst 83:200–204, 1991]


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