Palmitate-derivatized antibodies can specifically "arm" macrophage effector cells for ADCC

The use of palmitate-derivatized antibodies (pal-Ab) for "arming" macrophage (M phi) effector cells for antibody-dependent cellular cytotoxicity (ADCC) is described. Pal-Ab were incorporated onto the M phi plasma membranes by insertion of the palmitate hydrocarbon chains into the outer leaflet of the phospholipid bilayer. M phi bearing pal-Ab specific for chicken erythrocytes (CE) mediated efficient destruction of the CE targets. Neither non-ADCC effector cell populations nor pal-Ab consisting of antibody F(ab')2 fragments effected significant CE lysis. M phi bearing pal-Ab that were not specific for CE did not mediate CE destruction, nor did anti-CE pal-Ab-bearing M phi lyse nonspecific human erythrocyte targets. In this system of effector cell arming, the palmitate anchor of pal-Ab allows for the incorporation of large numbers of antibodies onto the effector cell surface, where they can promote efficient target cell capture and engage preexisting or newly expressed FcR on the effector cell surface. The results in this study, together with those from previous and ongoing investigations in which F(ab')2 pal-Ab were shown to mediate Fc receptor (FcR)-independent cytotoxicity by natural killer (NK) cells and M phi populations at appropriate states of activation, suggest that pal-Ab, by directing both ADCC and FcR-independent effector cell activity onto a specified target, offer important advantages over other methods of effector cell arming.