ACCUMULATION ENHANCEMENT OF HUMAN MONOCLONAL-ANTIBODY HB4C5 TO LUNG-TUMOR XENOGRAFTS BY N-DEGLYCOSYLATION

The fractional uptake of intact monoclonal antibodies by tumors is rel atively low. Various methods to alter the molecular structure have bee n used to augment tumor uptake. These chemical manipulations, however, may alter the specificity of antibody binding. Methods: Comparative s tudies of biodistribution, radioimmunoimaging and macroautoradiography in LC-6 xenografted mice were conducted with the I-125-labeled intact and N-terminal deglycosylated monoclonal antibodies to evaluate the e ffect on deglycosylation on antibody binding. Results: The removal of N-glycosyl residues from this monoclonal antibody significantly enhanc ed specific localization of the radioactivity to the tumor, especially to its necrotic fraction. Nonspecific accumulation of radioactivity t o the necrotic fraction of the tumor was excluded by biodistribution s tudies demonstrating selective accumulation of I-125-labeled monoclona l antibody after coadministration of I-125-monoclonal antibody (intact or N-deglycosylated) with I-131-labeled control IgM. Conclusion: The lung cancer-associated human monoclonal antibody HB4C5, which recogniz es histone H2B as the antigen, accumulates specifically to the necroti c fraction of tumor. The uptake is enhanced by removal of N-terminal g lycosyl residues from the antigen-binding site of the light chain.