Correlation of catabolism and antigen shedding with monoclonal antibody uptake by human colon and lung tumor xenografts.
Catabolism of B6.2 and B72.3 monoclonal antibodies by human colon (LS174T) and lung (A549) tumor xenografts appears to be a variable and complex process. 125I-B72.3 and 125I-B6.2 bound to LS174T cells in vitro and localized in tumors in athymic mice. 125I-B6.2 bound to A549 cells in vitro, but did not localize in tumors. To understand these differences, tumors were grown around subcutaneously implanted micropore chambers and tumor fluid was analyzed for the presence of shed tumor antigen or functional antibody following intravenous injection. Up to two orders of magnitude lower functional B6.2 was detected in the A549 tumor fluid than in the LS174T tumor fluid. Also, A549 fluid almost totally (82-94%) inhibited binding of 125I-B6.2 to target cells in vitro due to free B6.2 antigen present in the chamber fluid. The micropore chambers utilized in this study have the potential for expanding our understanding of the way antibodies are metabolized in various types of tumors. Utility of an antibody in vivo cannot be entirely predicted from in vitro binding studies given that tumor related factors such as antibody transport, antibody catabolism and shed antigen may influence localization of antibodies in tumors. Monoclonal antibodies against nonshed antigens may prove to be more appropriate for cancer imaging and therapy.
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E.I. DuPont de Nemours, Co., Inc., Medical Products Department, North Billerica, Mass.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology*; D000941:Antigens / Q000276:immunology*; D002460:Cell Line; D003110:Colonic Neoplasms / Q000276:immunology*; D004591:Electrophoresis, Polyacrylamide Gel; D005110:Extracellular Space / Q000276:immunology; D006801:Humans; D007457:Iodine Radioisotopes / Q000032:analysis; D008175:Lung Neoplasms / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008851:Micropore Filters; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000941:Antigens; D007457:Iodine Radioisotopes