Monoclonal antibodies F36/22 and M7/l05 have been raised against human breast carcinoma cells. These antibodies localize human tumor xenografts which specifically express the corresponding target antigens. When passively administered, these McAbs produce a rapid and highly significant reduction in the volume of progressively growing human tumors implanted in athymic mice. The purpose of the proposed research is to extend these observations regarding the in vivo targeting and therapy of human tumor xenografts as generated both from primary tumor explants and characterized cell lines. The optimal therapeutic efficacies of passively-administered and drug-conjugated antibodies will be assessed regarding the following parameters, using tumor volume reduction as the endpoint: l) levels of antigen expression; 2) dosage and scheduling of antibodies; 3) initial tumor volume; 4) initial growth rate of the tumor; 5) the presence or absence of metastasis; and 6) the combined use of multiple McAbs. Studies on the ability of McAbs to deliver NMR-dense substances to tumor sites will also be performed. Using the tissue localization index as the endpoint, McAbs conjugated to iron-56 and fluorine-l9 metal chelates will be administered to animals bearing human tumor xenografts. McAbs will also be evaluated for their capacity to specifically remove carcinoma cells from bone marrow, as a pre-requisite for future autologous bone marrow rescue.
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