| dc.description | Eleven IgG murine monoclonal antibodies (MABs) to human mammary carcinoma (HMC), DAL-BR1 to DAL-BR11, have been characterized. Six of the 11 MABs belong to the IgG$\sb1$ subclass, one each to the IgG$\sb{\rm 2a}$ and IgG$\sb{\rm 2b}$ subclasses, and three to the IgG$\sb3$ subclass and all but 2 MABs, DAL-BR5 and 11, bear Kappa light chains. These MABs had a very restricted or no reactivity to normal human tissues and strong reactivity to 5 HMC, 1 renal carcinoma, 1 colonic carcinoma, and 3 melanoma cell lines but no reactivity to lymphoma, nephroblastoma, or prostatic carcinoma cell lines. An immunofluorescence assay using unfixed, frozen tissue sections showed that each MAB reacted with a variable number of 13 surgically excised HMC specimens and with a variable number of tumor cells in these specimens. Immunoperoxidase stained sections of formalin fixed, paraffin embedded tissues showed only DAL-BR7 staining most HMC as well as benign breast lesions and with the exception of DAL-BR6, which stained a small proportion of tumor cells in 3/5 melanoma cases, none of the MABs stained non-HMC tumors. DAL-BR6 and 7 immunoprecipitated an identical 47 Kd protein from surface radiolabeled target cell extracts and radiolabeled preparations of these 2 MABs showed partial competitive binding to this antigen. DAL-BR6 and 7 were also able to induce caps on HMC cells and were endocytosed after binding to their antigen. Four MABs (DAL-BR2, 3, 9 and 11) immunoprecipitated a protein from surface radiolabeled target cell extracts that ran as a 73 Kd band under reducing conditions but which was not iodinated. The target antigens of the MABs were sensitive to trypsin but not to neuraminidase and the MABs did not react with CEA, human milk fat globules, lactalbumin, lactoferrin, bovine kappa casein, and except for DAL-BR8, human casein. There was reduction in the reactivity of only DAL-BR6 and 7 to heat treated cells. None of the MABs were cytotoxic to HMC cells but DAL-BR2, 3, 4, 5, 8, 10 and 11 did inhibit the proliferation of these cells after a 6 hour pulse exposure. Methotrexate and Adriamycin conjugates of a few MABs also inhibited cell proliferation but at higher concentrations than observed with native drug. When injected into nude mice, radiolabeled DAL-BR5, 6, 7, 9, and 11 as well as the F(ab)$\sb2$ fragments of DAL-BR6 and 7 selectively localized in HMC xenografts. | en_US |
