TREATMENT OF NEUROBLASTOMA PATIENTS WITH ANTIGANGLIOSIDE GD(2) ANTIBODY PLUS INTERLEUKIN-2 INDUCES ANTIBODY-DEPENDENT CELLULAR CYTOTOXICITYAGAINST NEUROBLASTOMA DETECTED IN-VITRO

Therapy of neuroblastoma patients with interleukin (IL)-2 activates ef fector cells capable of lysing tumor cells in vitro. When tumor cells are pretreated with certain monoclonal antibodies (MoAb), these in viv o activated effecters show augmented tumor lysis via antibody-dependen t cellular cytotoxicity (ADCC). This study presents immunological anal yses of serial blood samples from two refractory neuroblastoma patient s who received combined in vivo therapy with murine anti-ganglioside G D(2) monoclonal antibody 14.G2a and IL-2. These studies were designed to determine whether conditions that induce ADCC in vitro can be gener ated in vivo by combined therapy with IL-2 and MoAb. As shown previous ly, administration of IL-2 dramatically augments the ability of periph eral blood mononuclear cells (PBMC) to mediate ADCC. In addition, we d emonstrate here that sera, obtained 1 h after infusion of 14.G2a, prov ides an effective source of functional antibody for ADCC mediated by P BMC from healthy donors. Finally, effective ADCC-mediated killing of n euroblastoma target cells was also achieved in vitro following IL-2 pl us 14.G2a treatment when patients' effector cells were combined with p atients' serum, as the source of 14.G2a antibody. These results indica te that this combination of IL-2 and 14.G2a generates conditions withi n the peripheral blood of pediatric neuroblastoma patients that enable their own lymphocytes to mediate antibody-dependent cellular cytotoxi city sufficient to effectively kill neuroblastoma cells in vitro.