Fusion Partners for Production of Human Monoclonal Antibodies

Abstract

The technology for production of murine monoclonal antibodies has advanced enormously since its introduction by Kohler and Milstein (1975). However, the production of human monoclonal antibodies by fusion technologies has been hampered, mainly by the current scarcity of suitable human cell lines as fusion partners. Hypoxanthine-aminopterin-thymidine (HAT)-sensitive murine plasmacytomas have been fused with human lymphocytes to yield mouse-human hybrids that secrete human antibody against the Forssman antigen (Nowinski et al., 1980), keyhole limpet hemocyanin (KLH) (Lane et al., 1982), tetanus toxoid (Kozbor et al.,1982b; Butler et al., 1983), human tumor-associated antigen (Schlom et al.,1980; Sikora and Wright, 1981; Sikora and Phillips, 1981), and multiple endocrine organs (Satoh et al., 1983). These interspecies hybridomas preferentially segregate human chromosomes, making it difficult to derive stable lines secreting human antibody. However, the loss of human chromosomes from mouse-human hybridomas is not random. It is known, for example, that human chromosomes 14 (heavy chain) and 22 (λ light chain) are preferentially retained, whereas chromosome 2 (κ chain) is preferentially lost (Croce et al.,1979; Erikson et al., 1981).