In vitro mimicry of CaMBr1 tumor-associated antigen by synthetic oligosaccharides.
The murine monoclonal antibody (Mab) MBr1, raised against the breast cancer cell line MCF7, recognizes a saccharidic epitope overexpressed on a high percentage of human breast, ovary, and lung carcinomas. This antigen was originally identified on the immunogen as a globo-series glycosphingolipid with an H-like determinant at its terminus (globo-H). We report here the biological characterization of the entire globo-H hexasaccharide and five synthetic oligosaccharides representing fragments of the entire structure and/or different anomeric configurations. Using competitive binding assays on live cells, we identified the residues and the linkages essential for mimicry of the cellular antigens recognized by Mab MBr1 on the breast carcinoma cell line MCF7 and small cell lung cancer cell line POVD. The terminal tetrasaccharidic fragment of globo-H is the oligosaccharide that most resembles the MBr1-defined epitope both on glycolipids and on glycoproteins. This information will help in the rational design of a highly specific reagent for active specific immunotherapy of carcinomas overexpressing the MBr1-defined antigen.
Adobati
E
E
Divisione di Oncologia Sperimentale E. Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy.
Panza
L
L
Russo
G
G
Colnaghi
M I
MI
Canevari
S
S
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000276:immunology*; D002240:Carbohydrate Sequence; D000939:Epitopes; D005260:Female; D005915:Globosides / Q000276:immunology; D006028:Glycosphingolipids / Q000276:immunology*; D006801:Humans; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D000939:Epitopes; D005915:Globosides; D006028:Glycosphingolipids; D009844:Oligosaccharides