So, the effectiveness of targeted anti-tumor immunotoxin 4D5scFv-PE40 based on HER2-specific antibody 4D5scFv and PE40 that we have shown previously is caused by target cell apoptosis and determined by combination of factors: (i) specific and affine binding of the immunotoxin to the HER2 receptor; (ii) effective internalization of the “receptor-immunotoxin” complex via clathrin-mediated endocytosis and (iii) productive intracellular transport of the immunotoxin providing delivery of functionally active PE fragment into the cytoplasm (Figure 6). The gene discussed is ERBB2; the disease is neoplasm.