Selective killing of tumor cells in vitro by immunotoxin composed of antitumor antibiotic streptonigrin and polyclonal specific antibodies

Streptonigrin N-hydroxysuccinimide ester (STN-COONSu) was obtained by carbodiimide synthesis. Poly- L-lysine (PLL) was loaded with STN-COONSu and conjugated to polyclonal rabbit immunoglobulin G (IgG) activated with sodium periodate. Non-specific IgG and IgG against Ehrlich carcinoma cells were used to construct non-specific and specific immunotaxins. Immunotaxins contained 100 molecules of streptonigrin per 1 molecule of IgG. The streptonigrin concentration that caused 50% of inhibition of [ 3H]thymidine incorporation in Ehrlich carcinoma cells (IC 50) was 0.8 μg/ml for specific immunotoxin, 16 μg/ml for non-specific immunotoxin, and 20 μg/ml for the poly- L-lysine-streptonigrin conjugate (PLL-STN) used as the initial water-soluble form of antibiotic. Our results demonstrate that the toxicity for target cells of streptonigrin conjugated to specific IgG was 25 times higher than that of the initial water soluble form of antibiotic. This specific immunotoxin was non-toxic for non-target cells.