Glycoproteins and glycolipids are important constituents of the cell surface of all mammalian cells, both normal and abnormal, many of which serve as antigens in autologous, syngeneic, and xenogeneic immunizations. They have been implicated in many other properties of cells that involve specific recognition and interactions. The main objective of this study is to analyze the surface glycoproteins and glycolipids from human melanoma and other human tumors. A series of mouse monoclonal antibodies (moAbs) to melanoma, astrocytoma, and renal cancer have been prepared; and the antigens recognized by some of these moAbs have been identified and partially characterized. Among the antigens showing relative restriction to malignant melanoma is a glycoprotein, gp13O, and a ganglioside, GD3. Melanomas are generally characterized by high levels of GD3 and GM3, with some melanomas having GM2 and GD2 in addition. Also being studied are antigens recognized by antibodies in patients' sera. FD antigen, which is confined to the autologous melanoma tumor, is a particularly interesting example of this class of antigen. Another antigen in this group is an antigen associated with pigmented melanomas. Unlike the other antigens studied, it is an internal antigen and appears to be a melanosomal component. Despite its internal localization it seems to be a good target for radiolocalization of melanoma in nude mice. Attempts to identify significant antigens in epithelial tumors are also underway. Many of these are mucin-like in nature and the antibodies recognize carbohydrate determinants. Glycolipids are also important antigens in various epithelial cancers. Also underway are most general biochemical studies on the nature of cell surface components of human cells and the significance of variation in their expression for differentiation and malignancy. (AG)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA021445-09
Application #
3165554
Study Section
Experimental Immunology Study Section (EI)
Project Start
1977-04-01
Project End
1988-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
9
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065
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Nagata, Y; Yamashiro, S; Yodoi, J et al. (1992) Expression cloning of beta 1,4 N-acetylgalactosaminyltransferase cDNAs that determine the expression of GM2 and GD2 gangliosides. J Biol Chem 267:12082-9
Lloyd, K O (1991) Humoral immune responses to tumor-associated carbohydrate antigens. Semin Cancer Biol 2:421-31
Furukawa, K; Arita, Y; Satomi, N et al. (1990) Tumor necrosis factor enhances GD3 ganglioside expression in cultured human melanocytes. Arch Biochem Biophys 281:70-5
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Lloyd, K O; Old, L J (1989) Human monoclonal antibodies to glycolipids and other carbohydrate antigens: dissection of the humoral immune response in cancer patients. Cancer Res 49:3445-51
Thampoe, I J; Furukawa, K; Vellve, E et al. (1989) Sialyltransferase levels and ganglioside expression in melanoma and other cultured human cancer cells. Cancer Res 49:6258-64
Furukawa, K S; Furukawa, K; Real, F X et al. (1989) A unique antigenic epitope of human melanoma is carried on the common melanoma glycoprotein gp95/p97. J Exp Med 169:585-90
Tai, T; Kawashima, I; Furukawa, K et al. (1988) Monoclonal antibody R24 distinguishes between different N-acetyl- and N-glycolylneuraminic acid derivatives of ganglioside GD3. Arch Biochem Biophys 260:51-5

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