Killing of human tumor cells in culture with adriamycin conjugates of human transferrin.

Receptors for human transferrin (Trf) in high density are found on reticulocytes and syncytiotrophoblast, but most unstimulated, normal adult cells do not bind Trf. In contrast, leukemia and breast adenocarcinoma cells have been shown to manifest Trf receptors, raising the possibility that these receptors might be employed to bind cytotoxic Trf conjugates. Trf was conjugated with adriamycin (Adr) and it was shown that the conjugates are bound by Trf receptors on plasma membranes of Daudi and HL-60 cells, following which Adr is identified in the nuclei of these cells. The biological effect of Adr is quantitated by the inhibition of tritiated thymidine uptake, and subsequent cell death is measured by trypan blue exclusion. The killing correlates directly with both the time of exposure and the amount of conjugate employed. These results suggest that such cytotoxic Trf conjugates hold promise for selective in vivo killing of some malignant cells.