STRUCTURAL CHARACTERIZATION AND IN-VIVO IMMUNOSUPPRESSIVE ACTIVITY OFNEUROBLASTOMA G(D2)

Shedding of neuroblastoma gangliosides is positively correlated with t umour progression in patients with neuroblastoma. In assessing the bio logical activity of these ganglioside molecules, we recently found tha t total human neuroblastoma gangliosides inhibit cellular immune respo nses. Here, we have studied the major neuroblastoma ganglioside, G(D2) G(D2) was purified by high performance liquid chromatography and stru cturally characterized by mass spectrometry. Immunoregulatory effects of G(D2) in vivo were then determined in an established murine model. G(D2) significantly downregulated the local cellular immune response t o an allogeneic cell challenge; the usual increase in mass of the lymp h node draining the injection site was reduced by 88%, from 1.52 to 0. 19 mg (control versus G(D2)-treated mice; p < 0.01). In parallel, lymp hocyte recovery from each node was also reduced from 2.4 to 1.2 x 10(6 ) cells, and lymphocyte DNA synthesis was reduced to half of the contr ol level. These results show that certain shed tumour gangliosides, su ch as G(D2), function as intercellular signalling molecules, downregul ate the cellular immune response, and may thereby enhance tumour forma tion and progression.