Accumulation enhancement of human monoclonal antibody HB4C5 to lung tumor xenografts by N-deglycosylation.
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 131I-labeled control IgM.


CONCLUSIONS
The lung cancer-associated human monoclonal antibody HB4C5, which recognizes histone 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.
Kusakabe
K
K
Department of Radiology, Tokyo Women's Medical College, Japan.
Kanaya
K
K
Sato
S
S
Kato
M
M
Mochizuki
K
K
Hashizume
S
S
Yasumoto
K
K
Murakami
H
H
Nomoto
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002294:Carcinoma, Squamous Cell / Q000276:immunology*; D006031:Glycosylation; D006082:Graft Enhancement, Immunologic; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal