ANTIGEN-SPECIFIC HUMAN MONOCLONAL-ANTIBODIES FROM MICE ENGINEERED WITH HUMAN IG HEAVY AND LIGHT-CHAIN YACS

We describe a strategy for producing human monoclonal antibodies in mi ce by introducing large segments of the human heavy and K light chain loci contained on yeast artificial chromosomes into the mouse germline . Such mice produce a diverse repertoire of human heavy and light chai ns, and upon immunization with tetanus toxin have been used to derive antigen-specific, fully human monoclonal antibodies. Breeding such ani mals with mice engineered by gene targeting to be deficient in mouse i mmunoglobulin (Ig) production has led to a mouse strain in which high levels of antibodies are produced, mostly comprised of both human heav y and light chains. These strains should provide insight into the adop tive human antibody response and permit the development of fully human monoclonal antibodies with therapeutic potential.