Correlation of Catabolism and Antigen Shedding with Monoclonal Antibody Uptake by Human Colon and Lung Tumor Xenografts

Abstract

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.

Studies on immune responses to Bordetella avium in turkeys

“…Paraocular fluids contain antibodies of different isotypes chiefly secreted from the plasma cells in regional glands (56) (168,191). Also, the labelling method used in catabolism studies might complicate the results.…”