ACTIVATION OF CELLULAR CYTOTOXICITY AND COMPLEMENT-MEDIATED LYSIS OF MELANOMA AND NEUROBLASTOMA-CELLS IN-VITRO BY MURINE ANTIGANGLIOSIDE ANTIBODIES MB-3.6 AND 14.G2A

Mouse monoclonal antibodies against tumour-associated gangliosides G(D 2) (14.G2a) and G(D3) (MB 3.6) were tested to mediate antibody-depende nt cellular cytotoxicity (ADCC) with various effector cells or complem ent-dependent cytolysis (CDC). We also evaluated the immunomodulating potential of interferons in combination with cellular cytotoxicity. Us ing effector : target (E/T) ratios of 40 : 1, ADCC with effector cells such as granulocytes or mononuclear blood cells was not detectable ag ainst melanoma cell lines GR, SK-MEL-28 and G-361 which preferentially express G(D3) and bind antibody MB 3.6. Neuroblastoma cell line SK-N- LO, which was used for comparative purposes, mainly expressed G(D2) an d the tumour cells were killed effectively after labelling with antibo dy 14.G2a. Granulocytes did not show significant killing of melanoma c ells by ADCC, but neuroblastoma cells were killed very efficiently. Pe ripheral blood mononuclear cells (PBMC) also failed to kill melanoma c ells. Interferon-beta slightly stimulated PBMC and increased killing o f neuroblastoma cells, but no additive effects with ADCC were detectab le. Incubation of target cells with interferons produced no significan t differences in susceptibility of the target cells to interferon-acti vated PBMC cytotoxicity. Despite the lack of effectiveness in mediatin g cellular cytotoxicity, G(D3) antibody MB 3.6 showed strong complemen t-dependent cytolysis in the presence of human plasma. There were rema rkable differences in individual activity and different susceptibility of the melanoma cell lines. We assume that CDC may have more activity against melanoma cells than cytotoxicity associated with various effe ctor cells.