GM-CSF Enhances 3F8 Monoclonal Antibody-Dependent Cellular Cytotoxicity

3F8 is a murine monoclonal IgG3 antibody specific for the tumor-associated antigen ganglioside G . Previous in vitro studies suggest that tumor regressions observed in a phase I clinical trial of 3F8 may be attributable to complement activation by 3F8 and to 3F8-dependent cellular cytotoxicity (ADCC) with lymphocytes. We now describe 3F8-mediated ADCC of G -positive tumor targets (melanoma and neuroblastoma) with human granulocytes and report that recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) enhanced this phenomenon. Cytotoxicity required binding of 3F8 to the low-affinity Fc receptor type III (CD1 6) on the granulocytes and was poor with tumor-binding monoclonal antibodies of other immunoglobulin (ie. non-lgG3) subclasses. GM-CSF (2 to 20 ng/mL) increased ADCC by 93% to 267% at limiting