The Generation of Human Monoclonal Antibodies and Their Use in the Analysis of the Humoral Immune Response to Cancer

Abstract

The discipline of cancer immunology can be defined as having two related but distinct aspects. The first is the search for antigens on tumor cells that might distinguish these cells from their normal counterparts, using immunologic methods. The second is the investigation of the ability of animals and humans to recognize and respond to their own tumors. The discovery that inbred strains of mice are able to recognize antigens expressed by chemically induced sarcomas (Gross, 1943; Foley, 1953; Prehn and Main, 1957) opened up both of these important areas of tumor immunology. Studies of cancer cells with heterologous antibodies, long thought to be the way in which antigens on tumors could best be studied (Bashford, 1913), have not, until quite recently, yielded much useful information. However, the use of mouse monoclonal antibodies as monovalent, heterologous probes has developed into a powerful approach to the serologic analysis of tumors, vastly increasing our knowledge about the antigenic phenotypes of cells (Dippold et al., 1980; Ueda et al., 1981; Papsidero et al., 1983). These reagents have already been applied to the histological diagnosis and definition of tumors, and to the localization and treatment of cancer in patients (Epenetos et al., 1982; Miller and Levy, 1981; Osborn and Weber, 1982; Houghton et al., 1985). Although the use of mouse monoclonal antibodies in vivo may be limited by their immunogenicity (Houghton et al., 1985; Miller et al., 1982), they have certainly secured a permanent niche in the armamentarium of the basic scientist, pathologist, and clinician interested in cancer.