Long-term production of human monoclonal antibodies by five human-mouse heterohybridomas in a serum-free medium

Four heterohybridomas (28K29, 27D57, ZLG40, and 29D38) secreting human mono clonal antibodies (MAbs) reactive with lung cancer cells and one heterohybr idoma (28B49) secreting an isotype-matched MAb (IgM, lambda) were adapted a nd tested for long-term MAb production in serum-free medium. Three typical serum-free media were first evaluated for this purpose, based on the MAb pr oductivity, cost, and ease of MAb purification with each, and Hybridoma-SFM , containing only insulin and transferrin as protein components, was select ed as the most appropriate. In this medium, all five heterohybridomas conti nued to proliferate and secrete MAb throughout test periods of 144 to 200 d ays. Achievement of this long-term, stable production may be attributed at least in part to the effects of extensive prior subcloning and to the predo minance of h-type light chains in the IgM antibodies produced by these hete rohybridomas. The results of this study provide the basis for development o f a process to produce large quantities of human MAbs, which may be useful for therapeutic or in viva diagnostic purposes.