Strategies in the development of human monoclonal antibodies

A high-efficiency, HAT-sensitive heteromyeloma fusion line CB-F7 has been developed from an 8-Azaguanin-treated Ig-non-secreting human X mouse heterohybridoma. The use of this line allowed us to produce human hybridomas more successfully by fusion of cell material from blood, lymph node or spleen. A polyspecific repertoire of IgM isotype was detected among the hybridomas obtained from the spleen. These IgM antibodies reacted with autoantigens as well as with foreign material. This naturally occurring repertoire may be of interest since it has anti-bacterial activity. The frequency of the occurrence of polyspecific antibody-producing hybridomas was high in the spleen. Apart from the detection of polyspecific IgM antibodies we did not find IgG-secreting hybridomas with anti-bacterial reactivity among thousands of initial lines derived from non-immunized persons. We therefore tried to fuse lymphocytes from donors, who were boosted with Tetanus Toxoid (TTd). A short and limited optimum time period at which the blood should be taken from the donors after boosting, was detected. Seven days after in vivo immunization high yields of IgG-anti-TTd-producing lines (239 out of 731 IgG-producers) were found. The methods of developing more efficient production of human monoclonal antibodies of a pre-defined specificity were discussed.