The proposed program is centered on the use of enzymatically sialylated chemically synthesized, oligosaccharides as immunogens in the search for tumor markers. We are aiming at the synthesis of defined carbohydrate units containing sialic acid that have been reported to be part of the tumor associated glyconjugate CA 125. The oligosaccharide, Gal 1-4(Fuc 1- 3)GlcNAcBeta1-6(NeuAc 2-3 GalBeta1-3)Ga1NAc has been reported to be contained on a pure glycoprotein that contains CA 125 activity (1). The sialic acid moiety is felt to be important for this activity. CA 125 is an ovarian tumor marker which shows promise of being prognostically useful. Currently we have available Ga1 beta 1-3 Ga1NAc-0-phenyl-N=N-BSA and Ga1 1-3 (Ga1NAc 1-6) GalNAc-O-phenyl-N=N-BSA and purified placental sialyltransferase as well as serum sialyltransferase to begin our studies on the marker. We propose to develop other structures related to CA 125 through an enzymatic approach. Availability of these artificial complex saccharides will allow us to develop highly specific, high titer antibodies through the use of the saccharides linked via the diazonium salt to bovine serum albumin. Use of small chemically defined oligosaccharide haptens provides an alternative to the need for monoclonal antibody development to study these tumor markers. Our experience in use of defined carbohydrate haptens as immunogens supports the fact that development of antibody to these sialylated antigens can be accomplished. The antibodies which we developed will be used to determine the presence of absence of the sialylated carbohydrate antigen in tumor and normal tissue. These tissues are available through the cooperation of the Pathology Department at Roswell Park Memorial Institute. Perchloric acids extracts are already available from over 25 different tissues. The antibodies will also be used in localization studies in nu/nu mice containing human tumors. Over 100 sera from different ovarian adenocarcinoma patients are already available and will be used to determine the diagnostic value of our antibodies.
| Matta, K L; Piskorz, C F; Abbas, S A et al. (1991) Synthetic antigens as immunogens: Part IV. Specificity of antisera developed to Gal beta 1-3(GlcNAc beta 1-6)GalNAc and GlcNAc beta 1-6GalNAc. Immunol Invest 20:525-37 |
| Diakun, K R; Matta, K L (1989) Synthetic antigens as immunogens: Part III. Specificity analysis of an anti-anti-idiotypic antibody to a carbohydrate tumor-associated antigen. J Immunol 142:2037-40 |
