Embryonic precancerous and cancerous human antigens recognized by monoclonal antibodies.

Abstract

Monoclonal antibodies produced after immunization of mice with human melanomas define protein antigens expressed not only by melanomas by also by other tumours of neural crest origin such as astrocytomas and neuroblastomas. Other monoclonal antibodies react with antigens expressed by melanomas and fetal but not adult human melanocytes. Cells of common naevi and of precancerous lesions such as dysplastic naevi share many antigens with melanomas but not with normal melanocytes. Unlike melanomas, naevi in tissue culture are characterized by a finite lifetime. Factors that are instrumental in malignant transformation of dysplastic naevi in vivo and are apparently lacking in the tissue culture system are currently under study. Monoclonal antibodies produced after immunizing mice with cells of human gastrointestinal carcinomas define glycolipid antigens. The carbohydrate structure of one of these antigens is lacto-N-fucopentaose III. This antigen is very strongly expressed by a variety of human tumours and in the immunoperoxidase assay the respective monoclonal antibody also binds to normal human epithelium. Another monosialoganglioside is an antigen expressed by cells of gastrointestinal tract tumours such as of the pancreas, stomach and large bowel and by cells of villous adenomas of the colon, but not by cells of normal colonic mucosa. Its carbohydrate is a sialylated Lea-active pentasaccharide (sialylated lacto-N-fucopentaose II). A hitherto undiscovered sialyltransferase, which may be involved in synthesis of this antigen from Lewis A glycolipid, is probably active in tumour tissue and at early stages of embryogenesis but not in normal adult tissue. Human tumours implanted in mice are destroyed by monoclonal antibodies showing binding specificities for the implanted tumour. Only monoclonal antibodies of IgG2a isotype show tumoricidal activity. Destruction of the tumour is mediated by macrophages which adsorb the IgG2a monoclonal antibody to an Fe receptor. The tumours can also be destroyed, in the presence of monoclonal antibodies, by human monocytes, which after maintenance in culture fore two weeks develop Fc receptors for mouse IgG2a antibody.