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Accumulation Enhancement of Human Monoclonal Antibody HB4C5 to Lung Tumor Xenografts by N-Deglycosylation

Department of Radiology, Tokyo Women's Medical College, Tokyo
Morinaga Institute of Biological Science, Yokohama
Kitakyushu Municipal Medical Center, Kitakyushu
Graduate School of Genetic Resources Technology, Kyushu University, Fukuoka
Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan

Correspondence: For correspondence contact: Susumu Sato, Morinaga Institute of Biological Science, 2-1-1 Shimosueyoshi, Taurumi-ku, Yokohama 230, Japan.

Correspondence: For reprints contact: Kiyoko Kusakabe, MD, Dept. of Radiology, Tokyo Women's Medical College, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162, Japan.

ABSTRACT

The fractional uptake of intact monoclonal antibodies by tumors is relatively low. Various methods to alter the molecular structure have been used to augment tumor uptake. These chemical manipulations, however, may alter the specificity of antibody binding. Methods: Comparative studies of biodistribution, radioimmunoimaging and macroautoradiography in LC-6 xenografted mice were conducted with the ¹²⁵I-labeled intact and N-terminal deglycosylated monoclonal antibodies to evaluate the effect on deglycosylation on antibody binding. Results: The removal of N-glycosyl residues from this monoclonal antibody significantly enhanced specific localization of the radioactivity to the tumor, especially to its necrotic fraction. Nonspecific accumulation of radioactivity to the necrotic fraction of the tumor was excluded by biodistribution studies demonstrating selective accumulation of ¹²⁵I-labeled monoclonal antibody after coadministration of ¹²⁵I-monoclonal antibody (intact or N-deglycosylated) with ¹²⁵I-labeled control IgM. Conclusion: The lung cancer-associated human monoclonal antibody HB4C5, which recognizes his tone H2B as the antigen, accumulates specifically to the necrotic fraction of tumor. The uptake is enhanced by removal of N-terminal glycosyl residues from the antigen-binding site of the light chain.

Key Words: lung cancer • monoclonal antibody • human • deglycosylation

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