Generation of a mouse strain that produces immunoglobulin kappa chains with human constant regions

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Science  19 Nov 1993:
Vol. 262, Issue 5137, pp. 1271-1274
DOI: 10.1126/science.8235658


Humanized antibodies are highly efficient as immunotherapeutic reagents and have many advantages over rodent antibodies. A mouse strain was generated by gene targeting to replace the mouse kappa light chain constant (C) region gene with the human C kappa gene. Mice homozygous for the replacement mutation (C kappa R) produced normal concentrations of serum antibodies, most of which carry chimeric kappa light chains, and mounted normal immune responses to hapten-protein conjugates. This technology provides a feasible option for the generation of high-affinity humanized antibodies by means of the powerful somatic hypermutation-selection mechanism.