Production of monoclonal antibodies against oligosaccharides coupled to protein

Abstract

Altered glycosyIation is widely observed in the glycoproteins produced by tumors. Comparative studies of the sugar chains of glycoprotein produced by malignant cehs and their normal counterparts will provide information on their alterations. It has aheady been shown that such information is useful for the development of the new diagnostic methods of tumors. For the detection of altered sugar chains, two groups of reagents, Iectins and monoclona1 antibodies, have been wideIy usedim4. Although some immobihzed lectin coIumns have been found to be useful for such purpose, the number of lectins is limited. Because innumerable monoclonal antibodies can be obtained, this reagent can afford more progress for the diagnosis of tumors than lectins. So far, monoclonal antibodies directed to the sugar chains of glycoproteins have been produced by immunizing mice with whole tumor cells. Because various antigenic determinants are expressed on tumor cells, it was necessary to screen tremendous number of antibodies to obtain a useful one. For the more effective production of monoclonal antibodies directed to the altered sugar chains produced in tumors, we have designed a new strategy. This includes elucidation of the exact structural alterations of the sugar chains of tumor glycoproteins, pick up several of the alterations that are considered to be effective for the diagnosis of tumors, and prepare monoclonal anti~dies against them. Comparative study of the sugar chains of human chorionic gonadotropins (hCGs) isolated from the urine of pregnant women5 and patients with trophoblastic diseases including hydatidiform mole6, invasive mole’, and choriocarcinoma6v8,9