Binding and internalization of human immunoglobulin G conjugated with melphalan (K18) to human tumor cell lines.

The binding and internalization of melphalan-conjugated human immunoglobulin G (K18) to human tumor cell lines were studied using 14C-K18 (IgG conjugated with 14C-melphalan) and were compared with those of 14C-melphalan. K18 and melphalan dose-dependently bound to tumor cells, and the saturation binding analysis revealed a receptor-mediated binding of K18 but not of melphalan, to tumor cells. Intracellular distribution of 14C-K18 differed from that of 14C-melphalan, but a DNA unwinding experiment using a hydroxylapatite column showed that 14C-melphalan or 14C-K18 bound to DNA. These results suggest that after being bound to receptors K18 may be internalized in a macromolecular form and degraded into peptide binding melphalan. Moreover, the quantity of K18 that bound to 7 different human tumor cell lines was significantly larger than those that bound to lymphocytes of normal donors. These results suggest that K18 may be beneficial for cancer chemotherapy.