Humanization of antibodies.
Humanization has played a fundamental role in the remarkable progress of antibodies as therapeutic reagents. Here we have reviewed the publications on antibody humanization since the first report on CDR grafting in the second half of the 1980's up to June 2007. We describe the two main trends in the field: rational and empirical methods to humanize antibodies. Rational methods rely on the so-called design cycle. It consists of generating a small set of variants, which are designed based on the antibody structure and/or sequence information, and assessing their binding or any other characteristic of interest. Rational methods include CDR grafting, Resurfacing, Superhumanization and Human String Content Optimization. In contrast to rational methods, empirical methods are based on generating large combinatorial libraries and selecting the desired variants by enrichment technologies such as phage, ribosome or yeast display, or by high throughput screening techniques. The latter methods rest on selection rather than making assumptions on the impact of mutations on the antibody structure. These methods include Framework Libraries, Guided Selection, Framework Shuffling and Humaneering.
Almagro
Juan C
JC
Centocor R and D, Inc. 145 King of Prussia Rd. Radnor, PA 19087, USA. jalmagro@cntus.jnj.com
Fransson
Johan
J
D000818:Animals; D000906:Antibodies / Q000737:chemistry* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000627:therapeutic use; D000915:Antibody Affinity; D001435:Bacteriophages; D001666:Binding Sites, Antibody; D003165:Complement System Proteins / Q000737:chemistry; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D007135:Immunoglobulin Variable Region; D007158:Immunologic Techniques; D051379:Mice; D019151:Peptide Library; D015202:Protein Engineering / Q000379:methods*
D000906:Antibodies; D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007135:Immunoglobulin Variable Region; D019151:Peptide Library; D003165:Complement System Proteins