Impact of Light Chain Variants on the Expression of Therapeutic Monoclonal Antibodies in HEK293 and CHO Cells

Recombinantly produced monoclonal antibodies (mabs) belong to the fastest growing class of biotherapeutics. In humans, antibodies are classified into five different classes: IgA, IgD, IgE, IgG and IgM. Most of the therapeutic mabs used in the clinic belong to the IgG class, albeit other antibody-classes, e.g. IgM, have been evaluated in clinical stages. Antibodies are composed of heavy chains paired with a light chain. In IgM and IgA antibodies, an additional chain, the J-chain, is present. Two types of light chain exist in humans: The -light chain and the -light chain. The -light chain predominates in human and is used in the vast majority of therapeutically used IgGs. The reason for preference of the -light chain in human is not known. Our study investigates whether light chain selection influences productivity of the clinically validated mabs: adalimumab and trastuzumab. Both mabs were expressed as IgG and IgM with a  or a -light chain in HEK293 cells. Besides comparing the expression levels of the different mabs, we also evaluated, whether the passage number of the cell line has an impact on product yield. In addition, expression of adalimumab, trastuzumab, an anti-CD38 and an anti-PD-L1-antibody was analyzed in HEK293 and CHO cells when both, the κ- and λ-light chain are present. In summary, IgG outperformed IgM variants in expression efficacy while light chainselection had minimal impact on overall expression levels. Yields of all mab variants were higher in fresh cells, despite cell cultures with a high cell passage number having higher cell densities and cell numbers at the time of harvest. Incorporation of a particular light chain occurred at similar rates in HEK293 and CHO cells.