HIGHLY TUMOR-REACTIVE, INTERNALIZING, MOUSE MONOCLONAL-ANTIBODIES TO LEY-RELATED CELL-SURFACE ANTIGENS

Abstract

Two monoclonal antibodies, designated BR64 (IgG1) and BR96 (IgG3), were generated that, according to immunohistology, bind selectively to carcinomas of the colon, breast, ovary and lung. They have no or very low reactivity with normal human tissues, except for the fact that BR64 stains capillaries in the hearts from certain normal donors and that both monoclonal antibodies stain some epithelial cells from the gastrointestinal system, including stomach. Preliminary studies indicate that at least a portion of the epitope recognized by BR64 and BR96 is a Ley carbohydrate chain. Both monoclonal antibodies can be "internalized" by antigen-positive tumor cells, since immunoconjugates with ricin A-chain are cytotoxic. BR96 has the additional properties of being cytotoxic by itself, and it can mediate antibody-dependent cellular cytotoxicity and complement dependent cytotoxicity.