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CA 19-9 ganglioside antigen was extracted from the tumors of 16 patients with pancreatic cancer and the antigen was confirmed by mass spectrometry to be a sialyl Lewis(a) ganglioside. Ductal adenocarcinomas from four patients, two whose Lewis blood phenotype was Le(a- b-), one with undifferentiated carcinoma, and one with an acinar cell carcinoma, did not contain detectable amounts of sialyl Le(a) ganglioside. A significant correlation was found between serum CA 19-9 levels and the recovery of ganglioside antigen from respective tumors, but not tumor burden.

Mouse monoclonal IgM antibody (MAb 202) can cause melanoma cell necrosis in vivo. We analysed its immune mechanism in three melanoma patients to whom MAb 202 was administered. After the MAb 202 administration, histopathological analysis showed necrosis of melanoma cells expressing only GM3 in two patients. Another patient carrying both GM3 and GD3 showed infiltration of lymphocytes within the tumor nest but no tumor cells or nest necrosis. Immunohistological examination using anti-mouse IgM antibody revealed MAb 202 bound on the surface of melanoma cells in two patients but not in the third (positive for both GM3 and GD3). In vitro, MAb 202 reacted with the melanoma cells of the same two patients, but not with any other tissues of these individuals. We found no reaction of MAb 202 to non-melanoma cells including normal melanocytes and glia cells. Our trials suggest, 1) MAb 202 reacts directly to monosialogangliosides on the melanoma cell surface and then leads to the cytotoxicity reaction, or 2) MAb 202 induces lymphocyte infiltration and possibly then promotes the secretion of some cytokines.

A 52-year-old Japanese woman developed numerous amelanotic metastatic melanomas on the skin and in various organs three years after a surgical operation for primary melanoma on the right axilla. The patient was treated with monosialoganglioside specific monoclonal antibody 202; however, no apparent clinical effects were observed. Ganglioside analysis of a metastatic tumor demonstrated that it expressed GM3, GM2, GD3, GD2, and polysialogangliosides. Since polysialogangliosides rarely appear in melanomas, their expression may explain the patient's poor response to MAb 202. The relationship between ganglioside composition and the effect of anti-ganglioside monoclonal antibody is discussed.

Gangliosides of liposarcoma, lipoma and lipids from omental tissues were analyzed. By immunostaining after thin layer chromatography, gangliosides of liposarcoma were identified as GM3, sialylparagloboside and GD3, whereas those of lipoma were GM3 and GD3, and those of fat in omental tissues were GM3, GD1a, GD3 and some unknown ones. Expression of sialylparagloboside is thought to be very rare.

DU-PAN-2 reactive gangliosides were isolated from the tumor of a patient with pancreatic cancer (duct cell carcinoma, moderately differentiated adenocarcinoma), having a negative Lewis blood phenotype, and were analyzed by means of TLC-immunostaining, enzyme-linked immunosorbent assay (ELISA), permethylation study, 1H NMR spectroscopy and fast atom bombardment mass spectrometry. The structures of the gangliosides were found to be NeuAc alpha 2-3Gal beta 1-3GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1'Cer, containing normal and hydroxy fatty acids. By TLC-immunostaining and ELISA with chemically synthesized gangliosides, DU-PAN-2 was demonstrated to react strongly with IV3 alpha NeuAc-Lc4Cer, weakly with IV3 alpha NeuAc-nLc4Cer, and moderately with IV6 alpha NeuAc-Lc4Cer and IV6 alpha NeuAc-nLc4Cer. Thus it was concluded that the DU-PAN-2 reactive ganglioside in the tumor is IV3 alpha NeuAc-Lc4Cer and that DU-PAN-2 has a rather broad specificity.

The ganglioside patterns of erythrocytes from individual horses and cattle were examined. Variations in the ganglioside patterns were found in both horses and cattle. In the erythrocytes of most horses examined, NeuGc-Gal-Glc-ceramide (NeuGc-GM3) of 25 horses examined had only NeuGc-GM3 with no 4-O-Ac-NeuGc-GM3. The erythrocytes of various breeds of cattle had a characteristic ganglioside pattern, but they could be divided into 4 types on the basis of the composition of their gangliosides.

The glycolipids of erythrocytes from individual cats were examined. The main glycolipid of cat erythrocytes was generally NeuGc-NeuGc-Gal-Glc-ceramide (NeuGc-GD3), but among 41 cats of 5 breeds and 2 mongrels examined, 2 Persian cats were found to have NeuAc-NeuAc-Gal-Glc-ceramide (NeuAc-GD3). This is the first report of the occurrence of NeuAc-GD3 in cat erythrocyte membranes.

Mab 202, a mouse monoclonal IgM antibody which recognizes sialic acid alpha 2----3 galactosyl residue in monosialogangliosides and reacts with human melanoma cells but not with normal cells, was administered to a melanoma patient by either intralesional injection or intravenous infusion. Mab 202 induced regressions of the metastatic tumors without side effects. Histopathologic examination showed remarkable degenerative and necrotic changes in the tumor, around which lymphocytes, eosinophils, plasma cells and macrophages infiltrated. Immunoperoxidase staining revealed Mab 202 binding to melanoma cells. Clinical and pathologic evidence suggested that Mab 202 has cytotoxic effects against melanoma cells. Mab 202 may therefore be useful in the treatment of human malignant melanoma.

The gangliosides from the erythrocytes of various strains of inbred mice were analyzed. The ganglioside compositions differed in different strains and the strains could be divided into 4 types on the basis of this difference. The main ganglioside is GM4 or sialosyl galactosyl ceramide in Type 1, and unidentified ganglioside in Type 2, GM4 and GM2 in almost equal amounts in Type 3, and GM2 in Type 4.