Expression of antibody genes in nonlymphoid mammalian cells

A wide variety of mammalian cell lines have the ability to assemble and secrete immunoglobulins. This provides the possibility of adapting highly efficient mammalian cell expression systems available for nonlymphoid host cells to obtain efficient expression of recombinant antibodies. A set of vectors that use a powerful cytomegalovirus promoter enhancer to direct expression of the coding sequence for each immunoglobulin chain is described. The vectors also contain a replication origin from SV40 to generate high copy numbers in COS monkey kidney cells and a marker gene for selection of permanently transfected cell lines. Methods for generating microgram amounts of antibody in 2–4 days from COS cells and for stable introduction of the vectors into CHO cells are described. The use of a glutamine synthetase (GS) selectable marker to obtain vector amplification in CHO cells is also described. This permits the generation of cell lines that can accumulate in excess of 200 mg/liter of antibody in the culture medium.