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Gangliosides, sialic acid-containing glycosphingolipids, have engendered great interest for more than 20 years in the search for target molecules of relevance for tumour growth and formation of metastases and as potential targets for immunotherapy. These molecules show large quantitative and structural variability, which is related to cell type and developmental stage. Their potential role in the formation of tumour metastases was suggested from data supporting that they are involved in cell growth regulation and in cell-cell and cell-matrix adhesion. Moreover, gangliosides are expressed on the cell surface and thereby are accessible for antibodies or other ganglioside-binding molecules to induce cell death, inhibit cell growth and/or inhibit formation of tumour metastasis. All tumours exhibit aberrant ganglioside expression. This includes overexpression of normal ganglioside constituents, which appears to be common among various tumours, and expression of gangliosides not found in normal adult tissue but often found during fetal development. The ganglioside composition of melanoma cells has been found to correlate with their metastatic potential and also to be selectively expressed in cells of a tumour mass and invading tumour cells. Passive immunotherapy using murine or murine/human chimeric monoclonal antiganglioside antibodies in their native form or combined with various effector molecules has been investigated. However, the vaccination strategy using native or structurally modified tumour-associated gangliosides in combination with adjuvants is currently the dominant method in clinical trials. The outcomes reported so far vary between type of tumour and treatment strategies. However, we believe that targeting gangliosides is as promising as any other immune therapeutic strategy, and basic research as well as clinical trials utilising new aspects is encouraged.

Gangliosides on tumor cells have been suggested as potential target antigens for specific immunotherapy in various types of cancer including small cell lung cancer (SCLC). In this study we have compared the expression of three gangliosides that have been described as tumor-associated antigens, FucGM1, GM2 and GD3 in SCLC tissue specimens collected at autopsy, using a double-layer immunofluorescence staining method and specific monoclonal antibodies (Mabs) directed against these ganliosides. We found expression of FucGM1, GD3 and GM2 in (70% (n=20), 60% (n=15) and 40% (n75% of the tumor cells in all lesions from the same patient (five of eight cases). Our results indicate that FucGM1 is a relevant ganglioside antigen in SCLC, and suggest that specific immunotherapy involving more than one ganglioside antigen in SCLC should at least include FucGM1 and GD3.

The binding specificity of thirteen mouse monoclonal antibodies reacting with Fuc-GM1, Fuc alpha 1-2Gal beta 1-3GalNAc beta 1-4(NeuAc alpha 2-3)-Gal beta 1-4Glc beta 1-1Cer, a ganglioside found to be associated with small cell lung carcinoma (O. Nilsson et al. (1984) Glycoconjugate J. 1, 43-49) was studied. The results are based upon radioimmunodetection of their binding to structurally related glycolipids adsorbed to microtiter plates or chromatographed on thin-layer plates. Four of thirteen antibodies reacted only with Fuc-GM1 and both the fucose and the sialic residues were necessary for binding. Optimal binding was obtained when the sialic acid was N-acetylneuraminic acid. When this sialic acid residue was substituted with N-glycoloylneuraminic acid the binding activity was reduced and up to 10-times more Fuc-GM1 was needed for detection. The ceramide composition did not influence the binding. The other nine monoclonal antibodies cross-reacted with glycolipids containing structures closely related to Fuc-GM1 and differed from the specific ones by recognizing a smaller portion of the carbohydrate moiety in Fuc-GM1. These results indicate that anticarbohydrate monoclonal antibodies, recognizing structures involving a large proportion of the sugar in the glycolipid, possess a high specificity and might be useful for detection of tumor-associated ganglioside antigen.