Augmenting the cytotoxicity of oleic acid-protein complexes: Potential of target-specific antibodies

HAMLET (Human Alpha-Lactalbumin Made LEthal to Tumor cells), a complex of oleic acid (OA) with partially unfolded human α-lactalbumin, shows remarkable toxicity towards a spectrum of tumor cells as well as few differentiated cells including mammalian erythrocytes. Human erythrocytes, for this reason, have been used as convenient model cells to study toxic properties of the OA complexes. The toxicity of HAMLET-like complexes, prepared using immunoglobulin gamma (IgG) isolated from the sera of rabbits immunized with human erythrocytes as well as those unimmunized, towards the red cells was investigated. The OA complex of the IgG prepared by the heat-treatment procedure comprised of protein monomers and oligomers with bound OA. The IgG in the complexes retained most secondary but only partial tertiary structure and complex formation with OA did not abolish the ability of anti-erythrocyte IgG to bind to the erythrocytes. Anti-erythrocyte IgG-OA complexes were remarkably more hemolytic than those prepared using non-specific IgG, while complexes prepared using affinity purified anti-erythrocyte IgG were most effective in hemolyzing the cells. The work suggests that antibodies that exhibit affinity towards target cells may be useful in the preparation of selective and highly toxic OA complexes for the cells.