Antibody-Mediated Tumor Cytotoxicity of Microglia

Abstract

The status of microglial cells as potent effector cells in antibody-mediated tumor cytotoxicity (ADCC) could be established. Microglia (≧99.9% pure) derived from brain cortices of newborn mice were shown to lyse human tumor cell lines expressing different levels of epidermal growth factor (EGF) receptors in the presence of MAb 425, a monoclonal murine anti-primate EGF receptor antibody. MAb 425 mediates microglial ADCC (MiADCC) at concentrations as low as 10-11M. Antibody ligands binding unilaterally to either EGF receptors on target cells or Fc receptors on microglia have little effect on MiADCC. At 10-10M MAb 425, a 103-fold excess of MAb 425 F(ab’)2 fragments or irrelevant antibodies of identical isotype did not block MAb-425-induced MiADCC. Formation of effector-target cell contacts seems to be critical for MiADCC and MiADCC could not be inhibited by anti-tumor necrosis factor-α antibodies. In addition to its stimulatory effect on MiADCC, MAb 425 bound to EGF receptors exerted a microgliotrophic effect. Factor(s) derived from astrocytes enhance MiADCC.