Rodent to human antibodies by CDR grafting

Abstract The concept that a functional human-like antibody could be created by graft ing the antigen binding complementarity determining regions (CDRs) from variable domains of rodent antibodies on to human variable domains was first demonstrated by Dr Greg Winter and his colleagues at the MRC Labo ratory for Molecular Biology in 1986 (1). Since then several different research groups have developed and improved the methods for designing and constructing humanized antibodies via CDR grafting (2). There are reports of at least 80 antibodies being humanized by CDR grafting and at least eight of these antibodies being evaluated in clinical trials (3, 4). This chapter describes the procedures currently used at the MRC Collaborative Centre to create a ‘reshaped human’ antibody from a mouse antibody via CDR grafting.