Human Hybridomas

Abstract

The potential of monoclonal antibodies (Mabs) as therapeutic agents has now been firmly established (1). Although the technology for the production of murine hybridoma Mabs has been refined enormously since it was introduced (2), the technology for generating human Mabs has until now lagged behind, chiefly because of the paucity of suitable human cell lines that can serve as fusion partners and support the secretion of immunoglobulin (Ig). Hypoxanthine/aminopterin/thymidine (HAT)-sensitive murine plasmacytomas have been fused with human lymphocytes to yield mouse x human hybrids that secrete human antibody against the Forssman antigen (3), keyhold limpet hemocyanin (KLH) (4), tetanus toxoid (TT) (5,6), human tumor-associated antigen (7–9), and multiple endocrine organs (10). 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 x human hybridomas is not random. It is known, for example, that human chromosomes 14 and 22, which bear the Ig heavy chain and λ light chain locus, respectively, are preferentially retained, whereas chromosome 2, bearing the κ chain locus, is preferentially lost (11,12).KeywordsHuman Monoclonal AntibodyTetanus ToxoidLymphoblastoid Cell LineFusion PartnerMyeloma Cell LineThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.