Strategies for Stable Human Monoclonal Antibody Production

Construction of Heteromyelomas, in Vitro Sensitization, and Molecular Cloning of Human Immunoglobulin Genes
  • Gregory R. Reyes
  • Marcia Bieber
  • Kirk E. Fry
  • Kit S. Lam
  • Joan M. Hebert
  • Nelson N. H. Teng


The development of hybridoma technology by Köhler and Milstein (1975) opened a new era not only in immunology, but in all fields of biological science. Hybridoma cell lines formed by the fusion of mutant mouse myeloma cells with spleen cells from an immunized mouse assure the permanent availability of monoclonal antibody of defined specificity. The clinical use of these xenoantibodies in human patients, however, will be limited by the fact that they themselves will be immunogenic upon repeated administration. Accordingly, for therapeutic applications in man, the availability of human monoclonal antibodies would be advantageous. The advance of human hybridoma technology has, however, been slowed by the unavailability of suitable fusion partners. Early attempts to generate immortalized human immunoglobulinproducing cells involved the fusion of human lymphoid cells with mouse myeloma cells to create chimeric hybridomas (Levy and Dilley, 1978; Schwaber, 1975; Schwaber and Cohen, 1973). Although exceptions have been reported (Schlom et al., 1980; Lane et al., 1982), such mouse¡ªhuman hybridomas have tended to be unstable and cease immunoglobulin production due to the selective loss of human chromosomes (Weiss and Green, 1967; Nabholz et al., 1969), or to disturbances of gene expression (Raison et al., 1982). A second approach has involved the transformation of antigen-primed human B lymphocytes with Epstein-Barr virus (EBV) (Zurawski et al., 1978; Steinitz et al., 1979; Kozbor et al., 1979; Hirano et al., 1980; Tsuchiya et al., 1980; Yoshie and Ono, 1980). This method has also had some success, but in most instances, such cultures have tended to be unstable and produce low yields of antibody (Zurawski et al., 1978; Tsuchiya et al., 1980).


Myeloma Cell Tetanus Toxoid Hybrid Clone Hybrid Cell Line Mouse Myeloma Cell 
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Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Gregory R. Reyes
    • 1
  • Marcia Bieber
    • 1
  • Kirk E. Fry
    • 1
  • Kit S. Lam
    • 1
  • Joan M. Hebert
    • 1
  • Nelson N. H. Teng
    • 2
  1. 1.Cancer Biology Research Laboratory, Department of RadiologyStanford University School of MedicineStanfordUSA
  2. 2.Department of Gynecology and ObstetricsStanford University School of MedicineStanfordUSA

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