Discussion

Transgenic mice with human antibody repertoires were developed in the 1990s. These mice strains enabled development of several human monoclonal antibodies approved for use in the clinic. However, the technologies used at that time could not generate mice with full human repertoire. We took a different approach and moved these vast stretches of DNA into the correct place in a series of steps each with a smaller segment of DNA, carefully re-joining them and thereby re-constituting the complete human repertoire (5.4 Mb) in the mouse genome. These transgenic mice are viable and fertile, with an immune system resembling that of wild-type mice. Antigen immunization results in production of high affinity antibodies, broad epitope coverage and strong signatures of somatic hypermutation. This talk will demonstrate how the Kymouse™ provides a robust in vivo platform for the discovery of therapeutic human monoclonal antibodies and how, as a surrogate readout of the human antibody response, they may also aid vaccine development.