Improving the expression of chimeric antibodies following homologous recombination in hybridoma cells.

Mouse/human chimeric antibodies can easily be generated by exchanging the immunoglobulin constant gene segments with human sequences in mouse hybridoma cells by gene targeting. This obviates the need to isolate the variable gene regions from the hybridoma and permits high-level expression of chimeric antibodies, because the production rate of the hybridoma is often maintained. Here we show that the efficiency of this strategy can be further improved by increasing the number of high-producer clones arising from a recombination experiment. In principle, antibody production can be enhanced by removing the selection marker genes from the targeted cells.