IMR Press / FBL / Volume 13 / Issue 5 / 10.2741/2786

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Humanization of antibodies
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1 Centocor R&D, Inc. 145 King of Prussia Rd. Radnor, PA 19087
2 Centocor Discovery Research, San Diego, 3210 Merryfield Row. San Diego, CA 92121

Academic Editor: Biplab Bose

Front. Biosci. (Landmark Ed) 2008, 13(5), 1619–1633;
Published: 1 January 2008
(This article belongs to the Special Issue Antibody engineering)
Abstract

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.

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