Absolute Requirement of C D l l / CD 18 Adhesion Molecules , FcRII , and the Phosphatidylinositol - Linked FcRIII for Monoclonal Antibody - Mediated Neutrophil Antihuman Tumor Cytotoxicity

We have previously shown that 3F8, a murine IgG, monoclonal antibody (MoAb) specific for the ganglioside GD2, mediates tumor cell kill in vitro and in vivo. We now describe receptor requirements of polymorphonuclear leukocytes (PMN) in 3F8-mediated cytotoxicity (ADCC) of human G,(+) melanoma and neuroblastoma cell lines. PMN from a child with leukocyte adhesion deficiency (LAD) were devoid of CD11/CD18 adhesion molecules and mounted no detectable ADCC. MoAb to CDllb, CDllc, and CD18 each efficiently blocked ADCC by normal PMN. In contrast, a panel of different MoAbs to CDl la had no significant inhibitory effect on ADCC, a finding consistent with the low-to-absent expression of the CDl la ligand, intercellular adhesion molecule-1, on the target cells. Granulocyte-macrophage colony-stimulating factor (GM-CSF) significantly increased the expression of CDllb, CDllc, and CD18 on normal PMN, decreased the expression of Fc receptors (FcR), and enhanced ADCC by normal but not by LAD PMN. MoAbs to FcRll and FcRlll each